Advances in understanding drug metabolism and its contribution to variability in patient response

Recent advances in the understanding of the molecular biology and genetic v ariability of human drug metabolizing enzymes, particularly cytochromes P45 0, have contributed immensely towards clarifying the pharmacokinetics and p harmacodynamics of many existing drugs, and are increasingly important in t he development of new chemical entities. However, whereas this knowledge ha s implications for therapeutics, appreciation and application in clinical p ractice have either been limited or vet to be realized. For example, the de brisoquine polymorphism was discovered 20 years ago, but controlled prospec tive studies to evaluate its clinical significance and pharmacoeconomic imp act are few. Come the millennium it will be seen to what extent traditional therapeutic drug monitoring, involving the measurement of specific plasma drug concentrations, may be complemented or replaced by more general phenot yping or genotyping screens for human drug metabolizing enzymes.