Predicting inductive drug-drug interactions.
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.
Liddle
Christopher
C
Department of Clinical Pharmacology, Storr Liver Unit, Westmead Millennium Institute and University of Sydney, Westmead Hospital, Westmead, NSW 2145, Australia. chris_liddle@wmi.usyd.edu.au
Robertson
Graham R
GR
D000818:Animals; D002460:Cell Line; D002474:Cell-Free System; D000090702:Constitutive Androstane Receptor; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D004347:Drug Interactions / Q000235:genetics*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D000077297:Pregnane X Receptor; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology; D011987:Receptors, Steroid / Q000502:physiology; D020218:Response Elements; D014157:Transcription Factors / Q000502:physiology; D015262:Xenobiotics / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics*
D000090702:Constitutive Androstane Receptor; D000077297:Pregnane X Receptor; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D014157:Transcription Factors; D015262:Xenobiotics; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A