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142 Cards in this Set
- Front
- Back
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Mark whether the following statements is true (A) or false (B). Drug A is cleared only by hepatic metabolism and has an intrinsic clearance of 0.8 L/h
The oral bioavailability of this drug will be larger than 80%. |
True
Low extraction drugs (E < 0.2 and F > 0.8) have Clint * fu << QH |
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Mark whether the following statements is true (A) or false (B). Drug A is cleared only by hepatic metabolism and has an intrinsic clearance of 0.8 L/h
Plasma protein binding will affect the oral bioavailability of this drug. |
False
will affect the clearance of this drug. |
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Mark whether the following statements is true (A) or false (B). Drug A is cleared only by hepatic metabolism and has an intrinsic clearance of 0.8 L/h
The hepatic clearance of this drug is 1333 L/min |
False
Hepatic clearance can only be a maximum of 80 L/h |
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Mark whether the following statements is true (A) or false (B). Drug A is cleared only by hepatic metabolism and has an intrinsic clearance of 0.8 L/h
Plasma protein binding will affect the hepatic clearance of this drug. |
True
Plasma protein affects hepatic clearance in low extraction drugs but not in high extraction drugs. |
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Mark whether the following statements is true (A) or false (B). Drug A is cleared only by hepatic metabolism and has an intrinsic clearance of 0.8 L/h
Drug B, known to induce enzymes, also responsible for metabolism of Drug A, will significantly affect the clearance of Drug A. |
True
Enzyme induction is not affected in high extraction drugs because there is already a high amount of enzymes that are working. |
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Imagine a lipophilic unionized drug A with a volume of distribution of 108 L. When given by an iv bolus injection, the peak concentration of 0.18 µg/ml is observed (Co). When given orally, the oral bioavailability is 1.9 %. Plasma Protein Binding is 50% (fu=0.5).
Peak [µg/ml] 0.18 V [L] 108 F (%) 1.9 fu 0.5 The drug is highly metabolized in the liver. |
True
High extraction drugs are highly metabolized by liver due to first pass (and the majority of the drug being metabolized). In low extraction drugs it is the opposite. |
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Imagine a lipophilic unionized drug A with a volume of distribution of 108 L. When given by an iv bolus injection, the peak concentration of 0.18 µg/ml is observed (Co). When given orally, the oral bioavailability is 1.9 %. Plasma Protein Binding is 50% (fu=0.5).
Peak [µg/ml] 0.18 V [L] 108 F (%) 1.9 fu 0.5 Plasma protein binding will affect the oral bioavailability of this drug. |
True
Plasma protein binding affects oral bioavailability of high extraction drugs but not of low extraction drugs. |
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Imagine a lipophilic unionized drug A with a volume of distribution of 108 L. When given by an iv bolus injection, the peak concentration of 0.18 µg/ml is observed (Co). When given orally, the oral bioavailability is 1.9 %. Plasma Protein Binding is 50% (fu=0.5).
Peak [µg/ml] 0.18 V [L] 108 F (%) 1.9 fu 0.5 The hepatic clearance of this drug will be smaller than the Clren . |
False
Since drug is lipophilic and uncharged, Clren = urine flow * fu which will be smaller than hepatic clearance. |
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Imagine a lipophilic unionized drug A with a volume of distribution of 108 L. When given by an iv bolus injection, the peak concentration of 0.18 µg/ml is observed (Co). When given orally, the oral bioavailability is 1.9 %. Plasma Protein Binding is 50% (fu=0.5).
Peak [µg/ml] 0.18 V [L] 108 F (%) 1.9 fu 0.5 Plasma protein binding will affect the hepatic clearance of this drug. |
False
In high extraction drugs hepatic clearance is determined by liver blood flow (QH) only. |
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Imagine a lipophilic unionized drug A with a volume of distribution of 108 L. When given by an iv bolus injection, the peak concentration of 0.18 µg/ml is observed (Co). When given orally, the oral bioavailability is 1.9 %. Plasma Protein Binding is 50% (fu=0.5).
Peak [µg/ml] 0.18 V [L] 108 F (%) 1.9 fu 0.5 Drug B, known to induce enzymes that are also responsible for metabolism of Drug A, will significantly affect the clearance of Drug A. |
False
In high extraction drugs, enzyme induction does not affect clearance because there is already a high amount of enzymes working. |
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For the physiological changes listed below, select the induced changes on the pharmacokinetic parameters for a lipophilic acid (pKa=7.0), protein bound drug that is only eliminated through the kidneys (some answers may be used more than once). The pH of the urine is 7.0
Select the effect on kinetics (this effect should be clinically relevant) (A) Clren increases (B) Clren decreases (C) VD decreases (D) oral bioavailability F increases (E) nothing happens or effect is not listed Decrease in plasma protein binding |
(A) Clren increases
fu increases since Clren for unionized = urine flow * fu and Clren for ionized = GFR * fu. |
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For the physiological changes listed below, select the induced changes on the pharmacokinetic parameters for a lipophilic acid (pKa=7.0), protein bound drug that is only eliminated through the kidneys (some answers may be used more than once). The pH of the urine is 7.0
Select the effect on kinetics (this effect should be clinically relevant) (A) Clren increases (B) Clren decreases (C) VD decreases (D) oral bioavailability F increases (E) nothing happens or effect is not listed Decrease in urine pH |
(B) Clren decreases
The urine pH is more acidic and more unionized so Clren decreases since more drug is being reabsorbed after filtration. |
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For the physiological changes listed below, select the induced changes on the pharmacokinetic parameters for a lipophilic acid (pKa=7.0), protein bound drug that is only eliminated through the kidneys (some answers may be used more than once). The pH of the urine is 7.0
Select the effect on kinetics (this effect should be clinically relevant) (A) Clren increases (B) Clren decreases (C) VD decreases (D) oral bioavailability F increases (E) nothing happens or effect is not listed Increase in liver blood flow |
(E) nothing happens or effect is not listed
Does not affect Clren, Vd, or oral bioavailability |
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For the physiological changes listed below, select the induced changes on the pharmacokinetic parameters for a lipophilic acid (pKa=7.0), protein bound drug that is only eliminated through the kidneys (some answers may be used more than once). The pH of the urine is 7.0
Select the effect on kinetics (this effect should be clinically relevant) (A) Clren increases (B) Clren decreases (C) VD decreases (D) oral bioavailability F increases (E) nothing happens or effect is not listed Doubling in urine flow |
(A) Clren increases
or (E) nothing happens or effect is not listed Increases Clren for unionized and does not affect Clren for ionized |
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A drug is being cleared by the liver and kidneys. The drug is polar, has a molecular weight of 400 Dalton and is neither an acid nor a base. Plasma protein binding is 50% (fu=0.5). The oral bioavailability is determined by first pass and is 60%. Assume liver blood flow of 80 L/h, a GFR of 130 ml/min and a urine flow of 2 ml/min.
What is the hepatic clearance expressed in L/h. Values between 1 and 80 L/h. Express as full Liters/h ( 50 not 50.4 L/h). |
32 L/h
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A drug is being cleared by the liver and kidneys. The drug is polar, has a molecular weight of 400 Dalton and is neither an acid nor a base. Plasma protein binding is 50% (fu=0.5). The oral bioavailability is determined by first pass and is 60%. Assume liver blood flow of 80 L/h, a GFR of 130 ml/min and a urine flow of 2 ml/min.
What is the renal clearance expressed in mL/min. Values between 0 and 90 mL/min. Express as full mL/min (50 not 50.4 mL/min). |
65 mL/min
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A drug is being cleared by the liver and kidneys. The drug is polar, has a molecular weight of 400 Dalton and is neither an acid nor a base. Plasma protein binding is 50% (fu=0.5). The oral bioavailability is determined by first pass and is 60%. Assume liver blood flow of 80 L/h, a GFR of 130 ml/min and a urine flow of 2 ml/min.
What is the total clearance expressed in L/h. Values between 0 and 90 L/h. Express as full L/h (50 not 50.4 L/h). |
36 L/h
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A lipophilic acidic drug (pka of 7) is eliminated only by the kidney. Plasma protein binding is 90%. Glomerular filtration rate is normal (130 ml/min). Urine flow is 2ml/min. Urine pH is similar 7. The volume of distribution is 40L.
What value best describes the clearance? A: 0.15 mL/min B: 13 mL/min C: 130 mL/min D: 6.6 mL/min |
D: 6.6 mL/min
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Assume a one compartment body model? What is the renal clearance of a typical polar, (hydrophilic) drug showing 50% plasma protein binding. The patient has a creatinine clearance of 130 ml /min
A: 58.5 ml/min B: 130 ml/min C: 65 ml/min D: 6.5 ml/min E: 35.8 ml/min |
C: 65 ml/min
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Robert is very sick and needs treatment with an aminoglycoside. In order to start him on the aminoglycoside an iv bolus loading dose shall be given. Your responsibility is to give him the first dose. In order to do so, you have to estimate Robert’s creatinine clearance. Robert is 5 ft 10 inches tall, 34 years old, male, and weights 280 pounds. His serum creatinine is 1.5 mg/dl.
What creatinine clearance do you come up with? (Creatinine clearance between 1 and 99 mL/min. Use full numbers 51, not 50.7 mL/min) |
93 mL/min
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The renal clearance of a drug (as determined by filtration and reabsorbtion) always depends on the tissue binding of the drug.
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False
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The hepatic clearance of a drug is dependent on the plasma concentration of the drug in the body, as more drug can be metabolized when the plasma concentration of the drug is high.
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False
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For an acidic, lipophilic drug with a pka of 7.5, adjustment of the urine pH within physiological ranges will significantly change the renal clearance.
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True
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The larger the clearance of a drug, the smaller the AUC of a given drug.
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True
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Doubling the dose will generally double the AUC of a drug after iv bolus injection
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True
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Doubling the dose will generally double the AUC of a drug after iv bolus injection
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False
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The highest renal clearance will be similar to the kidney blood flow
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True
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Drugs with a renal clearance that is larger than GFR*fu are candidates for drug/drug interactions.
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True
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Which of the following statements is/are correct?
1) We can roughly assume that a change in clearance will result in a change in volume of distribution. 2) Drug A is 40% protein bound, drug B 98% protein bound. A two percent decrease in plasma protein binding will be most significant for drug A with respect to the clearance. 3) Genetic variability in metabolizing enzymes does always alter hepatic clearance. 4) In general, we should always use IBW for calculating creatinine clearance. A) 2, 3, 4 B) 1, 3 & 4 C) 2, 3 D) 3, 4 E) None of the above |
E) None of the above
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An investigational new drug is eliminated entirely by liver (hepatic) metabolism, with a clearance of 1.35 L/min in subjects with an average liver blood flow of 1.50L/min. What would be its expected clearance in a congestive heart failure patient with a liver blood flow of 1.10L/min but no change in hepatic extraction ratio?
A) 1.10L/min B) 1.50L/min C) 1.18L/min D) 0.99L/min E) Cannot be determined because the dose is not given. |
D) 0.99L/min
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Mark whether the following statements as true (A) or false (B). Drug A is cleared only by hepatic metabolism and has an intrinsic clearance of 80,000 L/h
The oral bioavailability of this drug will be larger than 80%. |
False
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Mark whether the following statements as true (A) or false (B). Drug A is cleared only by hepatic metabolism and has an intrinsic clearance of 80,000 L/h
Plasma protein binding will affect the oral bioavailability of this drug. |
True
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Mark whether the following statements as true (A) or false (B). Drug A is cleared only by hepatic metabolism and has an intrinsic clearance of 80,000 L/h
The hepatic clearance of this drug is 1333 L/min |
False
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Mark whether the following statements as true (A) or false (B). Drug A is cleared only by hepatic metabolism and has an intrinsic clearance of 80,000 L/h
Plasma protein binding will affect the hepatic clearance of this drug. |
False
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Mark whether the following statements as true (A) or false (B). Drug A is cleared only by hepatic metabolism and has an intrinsic clearance of 80,000 L/h
Drug B, known to induce enzymes also responsible for metabolism of Drug A, will significantly affect the clearance of Drug A if given together. |
False
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Imagine a lipophilic unionized drug A with a volume of distribution of 108 L. When given by an iv bolus injection, the a peak concentration of 0.18 μg is observed (Co). When given orally, the oral bioavailability is 99.9 %. Plasma Protein Binding is 50% (fu=0.5). This drug is a low extraction drug. E=0.001.
Peak [ug/ml] 0.18 V [L] 108 F (%) 99.9 fu 0.5 The drug is highly metabolized in the liver. |
False
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Imagine a lipophilic unionized drug A with a volume of distribution of 108 L. When given by an iv bolus injection, the a peak concentration of 0.18 μg is observed (Co). When given orally, the oral bioavailability is 99.9 %. Plasma Protein Binding is 50% (fu=0.5). This drug is a low extraction drug. E=0.001.
Peak [ug/ml] 0.18 V [L] 108 F (%) 99.9 fu 0.5 Plasma protein binding will affect the oral bioavailability of this drug. |
False
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Imagine a lipophilic unionized drug A with a volume of distribution of 108 L. When given by an iv bolus injection, the a peak concentration of 0.18 μg is observed (Co). When given orally, the oral bioavailability is 99.9 %. Plasma Protein Binding is 50% (fu=0.5). This drug is a low extraction drug. E=0.001.
Peak [ug/ml] 0.18 V [L] 108 F (%) 99.9 fu 0.5 The hepatic clearance of this drug will be smaller than the Clren. |
False
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Imagine a lipophilic unionized drug A with a volume of distribution of 108 L. When given by an iv bolus injection, the a peak concentration of 0.18 μg is observed (Co). When given orally, the oral bioavailability is 99.9 %. Plasma Protein Binding is 50% (fu=0.5). This drug is a low extraction drug. E=0.001.
Peak [ug/ml] 0.18 V [L] 108 F (%) 99.9 fu 0.5 Plasma protein binding will affect the hepatic clearance of this drug. |
True
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Imagine a lipophilic unionized drug A with a volume of distribution of 108 L. When given by an iv bolus injection, the a peak concentration of 0.18 μg is observed (Co). When given orally, the oral bioavailability is 99.9 %. Plasma Protein Binding is 50% (fu=0.5). This drug is a low extraction drug. E=0.001.
Peak [ug/ml] 0.18 V [L] 108 F (%) 99.9 fu 0.5 Drug B, known to induce enzymes also responsible for metabolism of Drug A will significantly affect the clearance of Drug A. |
True
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Imagine a lipophilic unionized drug A with a volume of distribution of 108 L. When given by an iv bolus injection, the a peak concentration of 0.18 μg is observed (Co). When given orally, the oral bioavailability is 99.9 %. Plasma Protein Binding is 50% (fu=0.5). This drug is a low extraction drug. E=0.001.
Peak [ug/ml] 0.18 V [L] 108 F (%) 99.9 fu 0.5 Drug B, known to induce enzymes that are also responsible for metabolism of Drug A is likely to decrease the clearance of A |
False
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For the physiological changes listed below, select the induced changes on the pharmacokinetic parameters for a hydrophilic strong acid, protein bound drug that is only eliminated through the kidneys (some answers may be used more than once).
“Strong acid” indicates that this drug will be mostly ionized at physiological pH. Select the effect on kinetics (A) Oral Bioavailability F↓ (B) Clren ↓ (C) VD ↑ (D) oral bioavailability F↑ (E) nothing happens or effect is not listed Decrease in plasma protein binding |
(C) VD ↑
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For the physiological changes listed below, select the induced changes on the pharmacokinetic parameters for a hydrophilic strong acid, protein bound drug that is only eliminated through the kidneys (some answers may be used more than once).
“Strong acid” indicates that this drug will be mostly ionized at physiological pH. Select the effect on kinetics (A) Oral Bioavailability F↓ (B) Clren ↓ (C) VD ↑ (D) oral bioavailability F↑ (E) nothing happens or effect is not listed Decrease in tissue binding |
(E) nothing happens or effect is not listed
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For the physiological changes listed below, select the induced changes on the pharmacokinetic parameters for a hydrophilic strong acid, protein bound drug that is only eliminated through the kidneys (some answers may be used more than once).
“Strong acid” indicates that this drug will be mostly ionized at physiological pH. Select the effect on kinetics (A) Oral Bioavailability F↓ (B) Clren ↓ (C) VD ↑ (D) oral bioavailability F↑ (E) nothing happens or effect is not listed Decrease in GFR |
(B) Clren ↓
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For the physiological changes listed below, select the induced changes on the pharmacokinetic parameters for a hydrophilic strong acid, protein bound drug that is only eliminated through the kidneys (some answers may be used more than once).
“Strong acid” indicates that this drug will be mostly ionized at physiological pH. Select the effect on kinetics (A) Oral Bioavailability F↓ (B) Clren ↓ (C) VD ↑ (D) oral bioavailability F↑ (E) nothing happens or effect is not listed Increase in urine flow |
(E) nothing happens or effect is not listed
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A lipophilic acidic drug (pka of 7) is eliminated only by the kidney. Plasma protein binding is 90%. Glomerular filtration rate is normal (130 ml/min). Urine flow is 2ml/min.Urine pH is similar to that of blood (about 7). The volume of distribution is 40L.
What value describes best the clearance? A: 0.15 mL/min B: 13 mL/min C: 130 mL/min D: 6.6 mL/min E: none of the above |
D: 6.6 mL/min
Fu=0.1 GRF*fu=13mL/min this drug has a significant portion unionized at physiological pH and therefore will undergo some reabsorption. If it were totally reabsorbed the clearance would be urine flow*fu=0.2 mL/min. However since our drug is ~50% ionized, only the uniozied half can be reabsorbed. So the clearance will be 6.5 ml/min which represents the 50% of the drug which undergoes filtration and is then trapped in the tubule (the ionized portion) plus a small amount which has the ability to be reabsorbed and is eliminated by urine flow. So the clearane will be a little bit higher than 6.5mL/min. |
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Assume a one compartment body model? What is the renal clearance of a typical aminoglycoside in a patient showing a creatinine clearance of 65 ml /min (10 points). The plasma protein binding for this aminoglycoside is 90 %.
A: 58.5 ml/min B: 130 ml/min C: 65 ml/min D: 6.5 ml/min E: 35.8 ml/min |
D: 6.5 ml/min
Clren=GRF*Fu=65 mL/min*0.1=6.5 mL/min. Aminoglycosides do not undergo reabsorption. |
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Robert is very sick and needs treatment with an aminoglycoside. In order to start him on the aminoglycoside an iv bolus loading dose shall be given. Your responsibility is to give him the first dose. In order to do so, you have to estimate Robert’s creatinine clearance. Robert is 5 ft 10 inches tall, 34 years old, male, and weights 280 pounds. His serum creatinine is 1.5 mg/dl. What creatinine clearance do you come up with?
A: 72 ml/min B: 84 ml/min C: 70 ml/min D: 103 ml/min E: none of the above |
E: none of the above
280 lbs/2.2=127.3 kg IBW=50+2.3*10=73 kg This patient is obese must use adjusted body weight in Creatinine clearance equation. ABW=73kg+0.4*(127.3-73)=94.7kg Clcr=(140-34)*94.7kg/(72*1.5 mg/dl)=92.9 mL/min |
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The following patients differ in the
Peak (mg/L) 0.60 / 0.60 Ke (1/h) 0.2 / 0.5 t1/2 (h) 2.9 / 1.4 AUC (mg/L*h) 2.50 / 1.25 (A) dose received (B) clearance (C) volume of distribution |
(B) clearance
The peak concentration is the same, which means that these patients were given the same dose and have the same Vd. Clearance must be different because the elimination rate is different. |
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The renal clearance of a drug (as determined by filtration and reabsorbtion) always depends on the tissue binding of the drug.
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False
Protein binding |
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To determine the clearance of a drug, one needs to know whether the drug is a one or two compartment drug.
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False
It is possible to use noncompartmental models. |
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Drinking a lot of water (urine flow is doubled) will increase significantly the renal clearance of aminoglycocsides.
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False, these drugs do not undergo reabsorbtion.
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For an acidic drug with a pka of 1.0, adjustment of the urine pH within physiological ranges will significantly change the renal clearance.
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False, the pKa will always be outside physiological range.
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Hepatic clearance depends on the drug plasma concentration, as the rate of metabolism increases with increasing drug concentrations in the blood.
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False, clearance is set for a certain drug.
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The larger the volume of distribution, the smaller the AUC of a given drug.
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False
AUC relates to CL, which is independent of Vd. |
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Doubling the dose will generally double the AUC of a drug after iv bolus injection.
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True
this is due to dose dependent or linear pharmacokinetics. |
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An increase in plasma protein binding will always result in a decrease of the drug’s hepatic clearance.
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False
Not for a high extraction drug. |
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An increase in plasma protein binding will under no circumstances result in a decrease of the drug’s hepatic clearance.
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False
It would for a low extraction drug. |
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Which of the following statements are correct?
1) We can roughly assume that a change in clearance will result in a change in volume of distribution. 2) Drug A is 40% protein bound, drug B 98% protein bound. A two percent decrease in plasma protein binding will be most significant for drug A. 3) Genetic variability in metabolizing enzymes always alters hepatic clearance. 4) In general, we should always use IBW for drug recommendations for calculating creatinine clearance (CLcr). A) 2, 3, 4 B) 1, 3 & 4 C) 2, 3 D) 3, 4 E) None of the above |
E) None of the above
1) These are independent parameters. 2) When looking at clearance of a low extraction drug a two percent change in fu will give a clearance twice as large. 3) Not for high extraction drugs. 4) Not if TBW is <120%IBW, then we use TBW. |
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An investigational new drug is eliminated entirely by liver (hepatic) metabolism, with a clearance of 1.35L/min in subjects with an average liver blood flow of 1.50L/min. What would be its expected clearance in a congestive heart failure patient with a liver blood flow of 1.10L/min but no change in hepatic extraction ratio?
A) 1.10L/min B) 1.50L/min C) 1.18L/min D) 0.99L/min E) Cannot be determined because the dose is not given. |
D) 0.99L/min
Since this drug is entirely eliminated by the liver you can set up a simple ratio. 1.35L/min/ 150L/min=X/1.10L/min X=0.99L/min |
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Mark whether the following statements as true or false for drug A, which is cleared only by hepatic metabolism and has a CLtot of 80 L/h
This drug is a low extraction drug |
False
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Mark whether the following statements as true or false for drug A, which is cleared only by hepatic metabolism and has a CLtot of 80 L/h
The clearance of another drug eliminated only by the kidney (only filtered not re-absorbed) will be smaller than that of Drug A |
True
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Mark whether the following statements as true or false for drug A, which is cleared only by hepatic metabolism and has a CLtot of 80 L/h
The oral bioavailability of this drug will be significantly smaller than 80% |
True
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Mark whether the following statements as true or false for drug A, which is cleared only by hepatic metabolism and has a CLtot of 80 L/h
The oral bioavailability will depend on liver blood flow |
True
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Mark whether the following statements as true or false for drug A, which is cleared only by hepatic metabolism and has a CLtot of 80 L/h
Drug C, known to induce enzymes also responsible for metabolism of Drug A will significantly affect the clearance of Drug A |
False
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Imagine a high extraction drug that is only eliminated via hepatic metabolism. Two patients have been injected with the same dose of this drug. They show the following pharmacokinetic properties
Cmax [μg/ml] 0.18 / 0.18 Ke [1/h] 0.55 / 0.73 Vd [L] 108 / 108 CL [L/h] 56 / 80 F (%) 6 / 1 A list of physiological parameter is shown below. Identify the one physiological parameter that would explain all differences in above pharmacokinetic parameters. A. GFR B. fu C. fut D. Qhep or Clint |
D. Qhep or Clint
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For the physiological changes listed below, select the induced changes on the pharmacokinetic parameters for a lipophilic, unionizable (no acid or basic group in the molecule), protein bound drug that is eliminated only through the kidneys (some answers may be used more than once).
Select the effect on kinetics (A) ClREN ↑ (B) ClHEP ↓ (C) VD ↑ (D) oral bioavailability F↑ (E) factor not listed in A-D Decrease in plasma protein binding |
(A) ClREN ↑
or (C) VD ↑ |
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For the physiological changes listed below, select the induced changes on the pharmacokinetic parameters for a lipophilic, unionizable (no acid or basic group in the molecule), protein bound drug that is eliminated only through the kidneys (some answers may be used more than once).
Select the effect on kinetics (A) ClREN ↑ (B) ClHEP ↓ (C) VD ↑ (D) oral bioavailability F↑ (E) factor not listed in A-D Increase in tissue binding |
(C) VD ↑
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For the physiological changes listed below, select the induced changes on the pharmacokinetic parameters for a lipophilic, unionizable (no acid or basic group in the molecule), protein bound drug that is eliminated only through the kidneys (some answers may be used more than once).
Select the effect on kinetics (A) ClREN ↑ (B) ClHEP ↓ (C) VD ↑ (D) oral bioavailability F↑ (E) factor not listed in A-D Decrease in liver blood flow |
(E) factor not listed in A-D
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For the physiological changes listed below, select the induced changes on the pharmacokinetic parameters for a lipophilic, unionizable (no acid or basic group in the molecule), protein bound drug that is eliminated only through the kidneys (some answers may be used more than once).
Select the effect on kinetics (A) ClREN ↑ (B) ClHEP ↓ (C) VD ↑ (D) oral bioavailability F↑ (E) factor not listed in A-D Increase in urine flow |
(A) ClREN ↑
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(Assume GFR is 130 mL min-1, urine flow is 1.5 ml min-1) For the following situations, indicate whether the drug is:
(A) filtered (B) reabsorbed (C) actively secreted (D) reabsorbed through transporters A drug with fu = 0.02and a ClREN = 20 mL min-1 is |
(C) actively secreted
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(Assume GFR is 130 mL min-1, urine flow is 1.5 ml min-1) For the following situations, indicate whether the drug is:
(A) filtered (B) reabsorbed (C) actively secreted (D) reabsorbed through transporters A drug with fu = 0.40 and a ClREN = 52 mL min-1 is |
(A) filtered
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(Assume GFR is 130 mL min-1, urine flow is 1.5 ml min-1) For the following situations, indicate whether the drug is:
(A) filtered (B) reabsorbed (C) actively secreted (D) reabsorbed through transporters A drug with fu = 0.60 and a ClREN = 0.9 mL min-1 is |
(B) reabsorbed
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(Assume GFR is 130 mL min-1, urine flow is 1.5 ml min-1) For the following situations, indicate whether the drug is:
(A) filtered (B) reabsorbed (C) actively secreted (D) reabsorbed through transporters A drug with fu = 1.0 and a ClREN = 0.3 mL min-1 is |
(D) reabsorbed through transporters
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A hydrophilic drug (predominantly ionized at pH=7.4) is eliminated only by the kidney. Plasma protein binding is 90%. Glomerular filtration rate is normal (130 ml/min). Urine flow is 2ml/min. No active renal secretion or active reabsorption after renal filtration is observed. The volume of distribution is 40 L.
What is the clearance? A. 0.15 mL/min B. 13 mL/min C. 1 mL/min D. 130 mL/min |
B. 13 mL/min
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Assume a one compartment body model? What is the renal clearance of a typical aminoglycoside in a patient showing a creatinine clearance e of 65 ml /min(10 points). The plasma protein binding for this aminoglycoside is 55 %.
A. 58.5 ml/min B. 130 ml/min C. 65 ml/min D. 29.3 ml/min E. 35.8 ml/min |
D. 29.3 ml/min
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Robert is very sick and needs treatment with an aminoglycoside. In order to start him on the aminoglycoside an iv bolus loading dose shall be given. Your responsibility is to give him the first dose. In order to do so, you have to estimate Robert’s creatinine clearance. Robert is 5 ft 10 inches tall, 34 years old, male, and weights 280 pounds. His serum creatinine is 1.5 mg/dl. What creatinine clearance do you come up with?
A. 72 ml/min B. 84 ml/min C. 93 ml/min D. 103 ml/min E. none of the above |
C. 93 ml/min
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See 2006 Exam 2 Question 18
The same dose of Alprazolam was given either alone or with ketoconazole. Explain what is going on by selecting the correct answer from the following list. 1: The clearance of alprazalam is increased in the presence of Ketoconazole. 2: Alprazalam is likely to be a low extraction drug. 3: Ketoconazole decreases the volume of distribution of Alprazolam, thereby increasing the half-life of the drug 4: Ketoconazole is likely to increase liver blood flow. The correct answer is: __________ A. 1 B. 2 C. 3, 4 D. 2, 3 E. 1, 2, 3, 4 |
B. 2
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The renal clearance of a drug depends the tissue binding of the drug.
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False
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The half-life of a drug increases with increasing tissue binding.
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True
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To determine the clearance of a drug, one needs to know whether the drug is a one or two compartment drug.
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False
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Drinking a lot of water (urine flow is doubled) will increase the renal clearance of aminoglycosides
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False
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For an acidic drug with a pka of 2.0, adjustment of the urine pH within physiological ranges will significantly change the renal clearance.
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False
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For a drug with linear pharmacokinetics, hepatic clearance depends on the drug plasma concentration, as the rate of metabolism increases with increasing drug concentrations in the blood.
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False
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The larger the volume of distribution, the smaller the AUC of a given drug.
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False
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Doubling the dose will double the AUC of a drug
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True
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An increase in fu will decrease AUC of a high-extraction drug given orally.
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True
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For a low extraction drug
Hepatic clearance will be larger than that of a high extraction drug |
False
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For a low extraction drug
Hepatic clearance will depend on liver blood flow |
False
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For a low extraction drug
Hepatic clearance will depend on tissue protein binding |
False
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For a low extraction drug
Oral bioavailability will be below 80% |
False
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For a low extraction drug
ke will not be affected by drugs that induce synthesis of the enzyme responsible for the metabolism of the low extraction drug |
False
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Imagine a low extraction drug that is only eliminated via hepatic metabolism. Two patients have been injected with the same dose of this drug. They show the following pharmacokinetic properties
Peak [ug/ml] 1.1 / 0.4 Ke [1/h] 0.6 / 0.4 V [L] 38 / 108 CL [L/h] 22.5 / 45.0 t1/2 [h] 1.17 / 1.66 A list of physiological parameter is shown below. Identify the one physiological parameter that would explain all differences in above pharmacokinetic parameters A. GFR B. fu C. fut D. Qhep E Clint |
B. fu
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For the physiological changes listed below, select the induced changes on the pharmacokinetic parameters for a lipophilic, unionizable (no acid or basic group in the molecule), protein bound high extraction drug that is also eliminated through the kidneys (some answers may be used more than once).
Select the effect on kinetics (A) ClREN ↑ (B) ClHEP ↓ (C) VD ↓ (D) VD ↑ (E) oral bioavailability F↑ Decrease (50%) in metabolic enzymes |
(E) oral bioavailability F↑
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For the physiological changes listed below, select the induced changes on the pharmacokinetic parameters for a lipophilic, unionizable (no acid or basic group in the molecule), protein bound high extraction drug that is also eliminated through the kidneys (some answers may be used more than once).
Select the effect on kinetics (A) ClREN ↑ (B) ClHEP ↓ (C) VD ↓ (D) VD ↑ (E) oral bioavailability F↑ Increase in tissue binding |
(D) VD ↑
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For the physiological changes listed below, select the induced changes on the pharmacokinetic parameters for a lipophilic, unionizable (no acid or basic group in the molecule), protein bound high extraction drug that is also eliminated through the kidneys (some answers may be used more than once).
Select the effect on kinetics (A) ClREN ↑ (B) ClHEP ↓ (C) VD ↓ (D) VD ↑ (E) oral bioavailability F↑ Decrease in liver blood flow |
(B) ClHEP ↓
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For the physiological changes listed below, select the induced changes on the pharmacokinetic parameters for a lipophilic, unionizable (no acid or basic group in the molecule), protein bound high extraction drug that is also eliminated through the kidneys (some answers may be used more than once).
Select the effect on kinetics (A) ClREN ↑ (B) ClHEP ↓ (C) VD ↓ (D) VD ↑ (E) oral bioavailability F↑ Increase in urine flow |
(A) ClREN ↑
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(Assume GFR is 130 mL min-1, urine flow is 1.5 ml min-1) For the following situations, indicate whether the drug is:
Select from the following choices: (A) filtered (B) reabsorbed (C) actively secreted (D) reabsorbed through transporters A drug with fu = 0.02and a ClREN = 20 mL min-1 is |
(C) actively secreted
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(Assume GFR is 130 mL min-1, urine flow is 1.5 ml min-1) For the following situations, indicate whether the drug is:
Select from the following choices: (A) filtered (B) reabsorbed (C) actively secreted (D) reabsorbed through transporters A drug with fu = 0.40 and a ClREN = 52 mL min-1 is |
(A) filtered
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(Assume GFR is 130 mL min-1, urine flow is 1.5 ml min-1) For the following situations, indicate whether the drug is:
Select from the following choices: (A) filtered (B) reabsorbed (C) actively secreted (D) reabsorbed through transporters A drug with fu = 0.40 and a ClREN = 52 mL min-1 is |
(B) reabsorbed
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(Assume GFR is 130 mL min-1, urine flow is 1.5 ml min-1) For the following situations, indicate whether the drug is:
Select from the following choices: (A) filtered (B) reabsorbed (C) actively secreted (D) reabsorbed through transporters A drug with fu = 1.0 and a ClREN = 0.3 mL min-1 is |
(D) reabsorbed through transporters
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A lipophilic drug (not an acid or base, that easily passes membranes) is eliminated only by the kidney. Plasma protein binding is 50%. Glomerular filtration rate is normal (130 ml/min). Urine flow is 2ml/min. No active renal secretion and active reabsorption after renal filtration is observed. The volume of distribution is 40 L.
What is the clearance? A: 1.0 mL/min B: 2.0 mL/min C: 4.0 mL/min D: 8.0 mL/min |
A: 1.0 mL/min
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What is the ke of the drug that has a volume of distribution of 100L and a clearance of 600 ml/min?
A: 6 min-1 B: 0.17 h-1 C: 27 h-1 D: 0.36 min-1 E: 0.36 h-1 |
E: 0.36 h-1
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Robert is very sick and needs treatment with an aminoglycoside. In order to start him on the aminoglycoside an iv bolus loading dose shall be given. Your responsibility is to give him the first dose. In order to do so, you have to estimate Robert’s creatinine clearance. Robert is 5 ft 10 inches tall, 34 years old, male, and weights 230 pounds. His serum creatinine is 1.5 mg/dl. What creatinine clearance do you come up with?
A 72 ml/min B 84 ml/min C 70 ml/min D 103 ml/min E 61 ml/min |
B 84 ml/min
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See 2005 Exam 1 Question 18
The same dose of Alprazolam was given either alone or with carbamazepine. Explain what is going on by selecting the correct answer from the following list. 1: The clearance of alprazalam is increased in the presence of carbamazepine. 2: Alprazalam is likely to be a low extraction drug. 3: Carbamazepine is an enzyme inhibitor. 4: Carbamazepine decreases liver blood flow. A: 1 B: 1, 2 C: 3, 4 D: 2, 3 E: 1, 2, 3, 4 |
B: 1, 2
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Assume the pH of urine to be 7, a glomerula filtration rate of 130 ml/min, a urine flow of 1.5 ml/min. For a basic drug (unionized form is very lipophilic, pka of the drug 7, plasma protein binding 50%, lacks affinity to transporters) that is only eliminated by the kidney, mark whether the following statements are true (A) or False (B)
The renal clearance will depend on the tissue binding of the drug. |
False
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Assume the pH of urine to be 7, a glomerula filtration rate of 130 ml/min, a urine flow of 1.5 ml/min. For a basic drug (unionized form is very lipophilic, pka of the drug 7, plasma protein binding 50%, lacks affinity to transporters) that is only eliminated by the kidney, mark whether the following statements are true (A) or False (B)
The renal clearance will be about 35 ml/min (about means +/-10%) |
True
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Assume the pH of urine to be 7, a glomerula filtration rate of 130 ml/min, a urine flow of 1.5 ml/min. For a basic drug (unionized form is very lipophilic, pka of the drug 7, plasma protein binding 50%, lacks affinity to transporters) that is only eliminated by the kidney, mark whether the following statements are true (A) or False (B)
The renal clearance of the drug will be about 65 ml/min |
False
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Assume the pH of urine to be 7, a glomerula filtration rate of 130 ml/min, a urine flow of 1.5 ml/min. For a basic drug (unionized form is very lipophilic, pka of the drug 7, plasma protein binding 50%, lacks affinity to transporters) that is only eliminated by the kidney, mark whether the following statements are true (A) or False (B)
Drinking a lot of water (urine flow is doubled) will increase the renal clearance by a factor of 2 |
True
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Assume the pH of urine to be 7, a glomerula filtration rate of 130 ml/min, a urine flow of 1.5 ml/min. For a basic drug (unionized form is very lipophilic, pka of the drug 7, plasma protein binding 50%, lacks affinity to transporters) that is only eliminated by the kidney, mark whether the following statements are true (A) or False (B)
Changing the pH of the urine to 6 will increase the clearance. |
True
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Assume the pH of urine to be 7, a glomerula filtration rate of 130 ml/min, a urine flow of 1.5 ml/min. For a basic drug (unionized form is very lipophilic, pka of the drug 7, plasma protein binding 50%, lacks affinity to transporters) that is only eliminated by the kidney, mark whether the following statements are true (A) or False (B)
Drug/drug interactions are likely for the elimination of this drug |
False
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Lipophilic unionized drugs are likely to enter tissues relatively fast.
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True
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The uptake of a hydrophilic drug into tissue can be increased significantly by increasing the blood flow through the tissue.
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False
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The volume of distribution will be reduced with increased clearance of a drug.
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False
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For a high extraction drug
Hepatic clearance will be larger than that of a low extraction drug |
True
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For a high extraction drug
Hepatic clearance will depend on liver blood flow |
True
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For a high extraction drug
Hepatic clearance will depend on plasma protein binding |
False
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For a high extraction drug
Oral bioavailability will be low |
True
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For a high extraction drug
Hepatic clearance will be determined by the GFR |
False
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See 2004 Exam 1 Question 6
Compare the following two concentration time profiles after a single bolus injection. The two lines differ in only one of the subsequent parameters. Please identify which parameter is different. The 2 lines differ in: Parameter A. Dose B. Vd C. Clearance |
B. Vd
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For the physiological changes listed below, select the induced changes on the pharmacokinetic parameters for a lipophilic, unionizable (no acid or basic group in the molecule), protein bound high extraction drug that is also eliminated by renal elimination (only filtration, no reabsorption).
(A) ClREN ↓ (B) ClHEP ↑ (C) oral bioavailability ↓ (D) VD ↑ E. none of the listed answers Increase in metabolic enzymes |
(C) oral bioavailability ↓
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For the physiological changes listed below, select the induced changes on the pharmacokinetic parameters for a lipophilic, unionizable (no acid or basic group in the molecule), protein bound high extraction drug that is also eliminated by renal elimination (only filtration, no reabsorption).
(A) ClREN ↓ (B) ClHEP ↑ (C) oral bioavailability ↓ (D) VD ↑ E. none of the listed answers Decrease in plasma protein binding |
(C) oral bioavailability ↓
or (D) VD ↑ |
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For the physiological changes listed below, select the induced changes on the pharmacokinetic parameters for a lipophilic, unionizable (no acid or basic group in the molecule), protein bound high extraction drug that is also eliminated by renal elimination (only filtration, no reabsorption).
(A) ClREN ↓ (B) ClHEP ↑ (C) oral bioavailability ↓ (D) VD ↑ E. none of the listed answers Increase in liver blood flow |
(B) ClHEP ↑
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For the physiological changes listed below, select the induced changes on the pharmacokinetic parameters for a lipophilic, unionizable (no acid or basic group in the molecule), protein bound high extraction drug that is also eliminated by renal elimination (only filtration, no reabsorption).
(A) ClREN ↓ (B) ClHEP ↑ (C) oral bioavailability ↓ (D) VD ↑ E. none of the listed answers Decrease in creatinine clearance |
(A) ClREN ↓
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(Assume GFR is 130 mL min-1, urine flow is 1.5 ml min-1) For the following situations, indicate whether the drug is:
Select from the following choices: (A) only filtered (B) filtered and reabsorbed through passive diffusion (C) filtered and actively secreted (D) filtered and reabsorbed through transporters A drug with fu = 0.04and a ClREN = 40 mL min-1 is |
(C) filtered and actively secreted
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(Assume GFR is 130 mL min-1, urine flow is 1.5 ml min-1) For the following situations, indicate whether the drug is:
Select from the following choices: (A) only filtered (B) filtered and reabsorbed through passive diffusion (C) filtered and actively secreted (D) filtered and reabsorbed through transporters A drug with fu = 0.20 and a ClREN = 26 mL min-1 is |
(A) only filtered
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(Assume GFR is 130 mL min-1, urine flow is 1.5 ml min-1) For the following situations, indicate whether the drug is:
Select from the following choices: (A) only filtered (B) filtered and reabsorbed through passive diffusion (C) filtered and actively secreted (D) filtered and reabsorbed through transporters A drug with fu = 0.30 and a ClREN = 0.45 mL min-1 is |
(B) filtered and reabsorbed through passive diffusion
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(Assume GFR is 130 mL min-1, urine flow is 1.5 ml min-1) For the following situations, indicate whether the drug is:
Select from the following choices: (A) only filtered (B) filtered and reabsorbed through passive diffusion (C) filtered and actively secreted (D) filtered and reabsorbed through transporters A drug with fu = 1.0 and a ClREN = 0.15 mL min-1 is |
(D) filtered and reabsorbed through transporters
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See 2004 Exam 1 Question 18
The same dose of triazolam was given either alone or with rifampin. Explain what is going on. Please choose the correct answers. 1: The clearance of triazolam is decreased in the presence of rifampin. 2: Triazolam is likely to be a high extraction drug. 3: Rifampin is an enzyme inducer. 4: Rifampin increases the volume of distribution of Triazolam. Select the correct answer A: 1 B: 1, 2 C: 3 D: 2, 3 E: 4 |
C: 3
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A drug is eliminated through glomerular filtration (no other clearance mechanisms is observed). It does not bind to plasma proteins. Glomerular filtration rate is normal (130 ml/min). No active renal secretion and passive or active reabsorption after renal filtration is observed. The volume of distribution is 50 L.
What is the clearance? A: 1.3 L/h B: 2.2 L/h C: 7.8 L/h D: 80 L/h |
C: 7.8 L/h
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What is the ke of the drug?
A: 0.044 h-1 B: 0.0260 h-1 C: 0.1560 h-1 D: 1.600 h-1 E: 0.390 h-1 |
C: 0.1560 h-1
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The nurses gave an iv bolus injection of an unknown drug at 7 a.m. They also did not record the dose. One hour after injection (8 a.m.) the concentration was found to be 6mg/L of plasma. Assume a ke of 0.150 h-1.
What would be the concentration at 8 pm? A 1.15 mg/L B 0.8 mg/L C 1.0 mg/L D 0.1 mg/L E 0.2 mg/L |
C 1.0 mg/L
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For a lipophilic unionized drug (no acid, or base)
The renal clearance will depend on the tissue binding of the drug. |
False
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For a lipophilic unionized drug (no acid, or base)
The renal clearance will depend on plasma protein binding. |
True
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For a lipophilic unionized drug (no acid, or base)
Drinking a lot of water will increase the renal clearance. |
True
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For a lipophilic unionized drug (no acid, or base)
Involvement of renal transporters in the renal elimination of the drug is likely. |
False
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For a lipophilic unionized drug (no acid, or base)
The renal clearance will be smaller than the GFR. |
True
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The tissue uptake of a lipophilic unionized drug is more likely to be perfusion controlled.
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True
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The degree of plasma protein binding affects the metabolic clearance of all drugs that are metabolized in the liver.
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False
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Increase in plasma protein binding will decrease the volume of distribution of a lipophilic drug.
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True
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The renal clearance of a highly ionized drug is more likely to be affected by drug/drug interactions.
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True
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Imagine a lipophilic unionized drug A with a volume of distribution of 108 L. When given by an iv bolus injection, the peak concentration of 0.18 µg/ml is observed (Co). When given orally, the oral bioavailability is 1.9 %. Plasma Protein Binding is 50% (fu=0.5).
Peak [µg/ml] 0.18 V [L] 108 F (%) 1.9 fu 0.5 Drug B, known to induce enzymes that are also responsible for metabolism of Drug A is likely to decrease the clearance of A. |
False
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