IN SUMMARY

Nonlinear pharmacokinetic behavior can result from saturable drug absorption, saturable protein binding, saturable drug metabolism or saturable renal excretion of the drug.

Nonlinear pharmacokinetics is characterized by disproportional change in the drug AUC after administration of increasing doses. Also, the average steady state conc achieved during multiple drug administration is not proportional to the dosing rate. The half life and total body clearance of drugs that follow nonlinear pharmacokinetics are different at different concentrations (conc-dependent).

Determination of the pharmacokinetic parameters and careful adjustment of the dosing regimen for drugs that follow nonlinear pharmacokinetics are necessary-because small change in the dosing rate can result in significant change in the drug concentration.