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46 Cards in this Set
- Front
- Back
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what are sufficient parameters to describe disposition of a drug?
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Cl & Vd
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what does Cl stand for?
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clearance
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Cl and Vd are sufficient parameters to describe what?
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drug disposition
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what is elimination?
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irreversible removal of drug from an animal by all routes
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what is the term for the irreversible removal of drug from an animal by all routes?
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elimination
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what is clearance?
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the volume of blood cleared of a substance per unit time
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what is the term for the volume of blood cleared per unit time?
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clearance
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how does clearance relate to elimination?
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clearance is a quantitative parameter used as a measure of elimination which includes metabolism (conjugation, hydrolysis, oxidation, reduction) and excretion
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what mechanisms are included in metabolism?
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conjugation, hydrolysis, oxidation, reduction
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conjugation, hydrolysis, oxidation and reduction are what type of mechanisms?
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metabolism
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what is the advantage of using clearance values?
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we can sum for all organs
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what are the units of clearance?
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L/hr
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what organs participate in clearance?
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primarily kidney and hepatic clearance, but also saliva, skin, blood, GI
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how does the kidney participate in clearance?
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mainly excretion (filtration & secretion) and some metabolism
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how does the liver participate in clearance?
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some excretion (bile) & mainly metabolism
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what affects organ clearance physiologically?
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effects of blood flow, binding, enzyme activity, secretory activity
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how do we determine organ clearance?
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assume drug in eliminating organ has reached distribution equilibrium: entry amount - extracted/excreted amount = exit amount
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illustrate clearance in the kidney?
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[renal A] - [urine] = [renal V]
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illustrate clearance in the liver?
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[hepatic portal V] - [bile] = [hepatic V]
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what is the extraction ratio?
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the fraction of bllod flow that can be cleared of a drug by that organ
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illustrated extraction ratio?
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rate of extraction / rate of presentation
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what is the range of ER for different organs?
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0-1 and differs for each organ
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what does the rate of presentation depend on?
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blood flow x concentration of plasma entering the organ
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what are the units for the rate of presentation?
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mg/hr
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what does the rate of extraction depend on?
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blood flow + plasma concentration difference across the organ
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what are the units for the rate of extraction?
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mg/hr
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what is the range for a highly extracted drug?
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0.7 < E < 1.0
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what is the range for an intermediate extracted drug?
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0.3 < E < 0.6
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what is the range for a low extracted drug?
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0.01 < E < 0.2
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illustrate clearance?
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rate of extraction/plasma concentration
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what is the physiological illustration of clearance?
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Cl = Q x ER
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what is the mathematical illustration of clearance?
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Cl (L/hr) = rate of excretion (mg/hr)/plasma concentration (mg/L)
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what does ER stand for?
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extraction ratio
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how is the rate of excretion related to the rate of infusion?
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Cl x plasma concentration so at equilibrium the rate of excretion = rate of infusion
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how does clearance change with increased plasma concentration?
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it does not change
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what is clearance a property of?
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of the organ and the drug
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how much can an organ clear?
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an organ can only clear a particular volume of blood of a drug per unit time
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illustrate clearanc in excretory products?
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Clorgan (L/hr) = [urine] (mg/L) / [plasma] (mg/L) x volume urine (L)/time (hr)
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what are common excretory products?
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urine, bile
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what physiological factors affect clearance?
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blood flow, protein binding, enzyme activity
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how does blood flow affect clearance?
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only affect high ER drugs resulting in flow-limited kinetics
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how are high ER drugs cleared? (general concept)
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efficiently
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how does protein binding affect clearance?
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only affects low ER drugs
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how does enzyme activity affect clearance?
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only affects low ER drugs
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high ER drug clearance is affected by what factor?
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blood flow
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low ER drug clearance is affected by what factor?
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protein binding, enzyme activity
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