Cytochrome P450 Enzymes, Drug Transporters and their Role in Pharmacokinetic Drug-Drug Interactions of Xenobiotics: A Comprehensive Review

Drug-Drug interactions (DDI) is a serious clinical issue. An important mechanism underlying of DDI, is induction or inhibition of drug metabolizing enzymes (DMEs) and transporters that mediate metabolism, cellular uptake and effl ux of xenobiotics. DDI cannot be avoided in many cases, as they belong to routine medical practice. Especially DMEs and transporters of small intestine, liver, kidney are the major determinants of the pharmacokinetic profi le of drugs. Enzymes and transporters mediated DDI in these three organs can considerably infl uence the pharmacokinetics and clinical effects of drugs. The purpose this review is to elucidate the effect of cytochrome P-450 (CYP 450) enzymes and transporters mediated DDI on the pharmacokinetics and further its clinical implications.