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17 Cards in this Set
- Front
- Back
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drug excretion
renal excretion |
most important for the majority of drugs
- glomerular filtration - active secretion (non-linear, carrier-mediated, for low drug concentrations can be linearized in the same way as the enzymatic rxn - tubular reabsorption |
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remaining excretion processes:
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are linear or can be linearized (biliary excretion) with respect to Ca
* except fecal excretion |
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clearance of excretion
here, the clearance due to excretion, Clx, is the summation of the clearances for: |
-glomerular filtration + CLf
-active secretion + Cls -tubular reabsorption - Clr other excretion processes + Clo +Clf, + Cls, -Clr = Clk |
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clearance of excretion
equation (10) |
- dnx/dt = Clx * ca
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drug elimination I
the total eliminated drug amount is: |
the sum of metabolized and excreted drug amounts
-dn/dt = dnm/dt - dnx/dt after substitution from 8 and 10 -dn/dt = (Clm + Clx) * ca |
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drug elimination II
the metabolic and excretion clearances: |
can be summed up
-dn/dt = Cl * ca cannot be integrated because of different variables: the eliminated drug amount n and the free drug concentration, ca. the same variable on both sides of 11 is needed |
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dose and free drug concentration I
the relation between n and ca can be found from: |
the definition of the partition coefficient (eq 5-1)
in each aqueous phase, the drug exists as free and bound to proteins (binding to enzymes is neglible) ci = ca +[DP]i |
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dose and free drug concentration II
for linear binding, the concentration of the drug/protein complex is: |
eq 6-2
[DP] = K * ca * po then the total drug concentration (free and bound) in the ith aqueous drug phase is: ci= ca + [DP]i= ca * (1+Ki * Pi) |
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dose and free drug concentration III
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see slide
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final equation
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see slide
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clearance
total clearance is: |
the sum of clearances for all elimination processes (eq 11)
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clearance of a process is:
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the rate constant of the process multiplied by the volume of the phase where the process takes place
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clearance equations
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see slide
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elimination rate constant I
from eq 14 |
ke = Cl/Vdf
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elimination rate constant is:
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the sum of individual rate constants weighted by the factor
volume of elimination phase/ distribution volume |
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elimination rate constant II
clearance can be summed up: |
regardless of the volume of the phase where the elimination is taking place
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elimination rate constant II
elimination rate constants can be summed up: |
only if the elimination processes take place in the same phase
otherwise, the individual rate constants have to be scaled (weighed) by the ratio of the phase volume and the distribution volume |
