Predicting inductive drug–drug interactions

Abstract

Until recently, inductive drug–drug interactions have proved difficult to predict prior to formal pharmacokinetic studies in man. Even then, important interactions have often gone unrecognized until clinical sequelae have occurred in the postmarketing phase. Recent advances in the molecular and cellular biology of nuclear receptors have revealed that there are ‘sensors’ for xenobiotics, which in turn transactivate genes involved in drug metabolism and excretion. Knowledge of these mechanisms has allowed the development of assay systems that detect the potential of drugs to cause gene induction, well before human studies are contemplated.