Hepatic drug metabolism and transport in patients with kidney disease

The disposition of many drugs is altered in patients with acute (AKD) and chronic kidney disease (CKD). A decline in renal clearance of several drugs has been correlated significantly with residual renal function (ie, creatinine clearance) of subjects. Reductions in nonrenal clearance of some compounds also have been reported and associated with clearance of markers of oxidative and/or conjugative metabolism or P-glycoprotein-mediated transport. Although initial accounts of reduced hepatic microsomal cytochrome P-450 (CYP) content and activity in animal models of AKD and CKD were published almost 25 years ago, it is only in the last decade that technical advances in molecular biology and clinical pharmacology have enabled researchers to begin to characterize the phenotypic expression of individual enzymes and, importantly, distinguish the molecular and/or genetic basis for these changes. The selective modulation of hepatic CYP enzyme activity observed in kidney disease is caused, at least in part, by differentially altered expression of several CYP isoforms. This review summarizes data available through June 2003 regarding the effect of AKD and CKD on drug metabolism. Knowledge of the impact and nature of these alterations associated with kidney disease may facilitate the individualization of medication management in this patient population.