Emerging in vitro tools to evaluate cytochrome P450 and transporter-mediated drug-drug interactions.
Drug-drug interactions comprise a significant cause of morbidity and mortality worldwide as they may lead to adverse clinical events, result in decrease/inactivation of the therapeutic effect of a drug, may enhance drug toxicity and indirectly compromise treatment outcomes and adherence. Drug transporters and drug metabolism enzymes govern drug absorption, distribution, metabolism, and elimination (ADME). Inhibition or induction of transporter and drug metabolism enzymes can alter the ADME of a co-administered drug, which may lead to drug-induced toxicity or lack of efficacy. This review assesses our current understanding of the in vitro methods of evaluating CYPs and transporter-mediated DDI. The DDI prediction models based on in vitro assays are also discussed in this review. The applications, advantages and limitations of each method are also addressed in this review.
Lu
Chuang
C
Drug Metabolism and Pharmacokinetics, Millennium Pharmaceuticals, Inc., 40 Landsdowne Street, Cambridge, MA 02139, USA.
Liao
Mingxiang
M
Cohen
Lawrence
L
Xia
Cindy Q
CQ
D000818:Animals; D001692:Biological Transport; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004347:Drug Interactions; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D008658:Inactivation, Metabolic; D026901:Membrane Transport Proteins / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010599:Pharmacokinetics
D026901:Membrane Transport Proteins; D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System