Kineticlass - Elimination

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Drug Elimination

KinetiClass (Ic)

Concepts

Organ clearance (hepatic clearance, renal clearance, etc.)
Total clearance (Clt, the sum of ALL organ clearances)
Half-life
Elimination rate constant
Effect of change in clearance on half-life, lz, Cave

Significance

Dysfunction of the organs of elimination (renal failure, hepatic failure, etc.) is associated with reduced clearance. Changes in volumes of distribution are usually small. Reduced total clearance changes the drugs half-life, average concentration and peak and trough concentration. Dosing in such patients should be done with some understanding of the effect of organ failure on the pharmacokinetics of the drug.

Exercise

1) Pharmacokinetic variables on the spreadsheet are preset for a typical adult horse given gentamicin.

2) For simulations #1 and #2

Leave the clearance value of simulation #1 as 0.12
Change the clearance value for simulation #2 to 0.06 l/kg/hr.

3) Simulations #3 and #4

Leave the clearance value of simulation #3 as 0.12
Change the clearance value for simulation #4 to 0.06 l/kg/hr

4) Review the calculated values at the bottom of the worksheet.

5) Review the graph of the simulations. Log Graphs can be viewed by clicking on the tab labeled "Log Graphs" at the bottom of the sheet. Notice the affects of the change in clearance between the two simulations.

Questions

1) Which plot (log or linear) best demonstrates the effect of a change in clearance on half-life?

2) Why are the peak concentrations (y axis intercepts) the same for simulations #1 and #2 ?

3) Why are the peak concentrations different for simulations 3 and 4 even though the absorption rates are the same?

4) Clearance of aminoglycosides is entirely by glomerular filtration (100% renal elimination). If patient #3 has normal renal function, what percentage of normal renal function would you predict for patient #4? (The answer also applies to the relationship between patients #1 and #2.)