Kineticlass - Distribution

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Volume of distribution

KinetiClass (Id)

Concepts

Volume of distribution (Vz)
Change in volume of distribution with fixed (unchanged) clearance

Significance

Disease processes (dehydration), physiologic states (neonates), or the addition of a "displacing" drug, may alter the volume of distribution of a drug. A change in the volume of distribution is a change in the volume of fluid that must be processed by the organs of elimination in order to remove the drug from the body. A change in the volume of distribution also changes the direct relationship between the amount of drug in the body and the plasma concentration (demonstrated most easily at time=0 following IV administration). Exercise

Exercise

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

2) Simulations #1 and #2

change the dose to 3 mg/kg
set the weight to any reasonable weight
change the interval to 6
Change the volume of distribution (Vz) for simulation #2 to 0.46
Make sure that the clearance values are the same (0.12) for both simulations

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

4) Review the linear and log graphs of the simulations.

Questions

1) Why does a change in the volume of distribution of a drug cause a change in the elimination rate constant and the half-life?

2) Does a longer half-life automatically tell you that the elimination processes have been impaired?

3) Which feature of the graphs tells you that the volumes of distribution have changed?

4) Calculate total clearance for simulation #1 and #2 from the volume of distribution and the half-life. (Use program "help" for formulas).