Drug-drug interactions with immunosuppressive agents: Review of the in vitro functional assays and role of cytochrome P450 enzymes

Frequency of drug-drug interaction is high in most solid organ transplant recipients because of polypharmacy. These interactions involve, predominantly, the cytochrome P450 (CYP) enzymes. Several reviews described these interactions, but few focused on how these interactions are evaluated. This review summarizes current in vitro functional assays of CYP activity to assist in understanding the bidirectional relationship between immunosuppressants and CYP enzyme system. To achieve our goal we describe the constituents of CYP system followed by discussing their role in the common immunosuppressive drug-drug interactions. We also present the various in vitro assays used to evaluate modulation of CYP enzyme activity.