Pharmacokinetic behavior presents drug therapy challenges.

There are conditions that cause a substantial change in drug clearance to such a degree that how a specific drug is managed to optimize drug response and minimize drug toxicity presents a challenge. This review will focus on recent literature (within the past 5 years) that evaluates pathophysiologic and genetic conditions and drug interactions which can change drug clearance to the magnitude that response is affected. Situations discussed that cause an increase in drug clearance will include: augmented renal clearance in critically ill patients; ultrafast drug metabolism caused by gene duplication; and enzyme induction interactions caused by rifampin. Situations discussed that result in a reduction in clearance will include: multiple organ failure in critically ill, patients with non-functioning CYP2D6 and CYP2C8/9 alleles, and CYP3A4 drug interactions with erythromycin and clarithromycin. In each case evaluated clearance is changed to the magnitude such that managing drug therapy can be difficult.