TY - JOUR T1 - What Can Be Learned from Recent New Drug Applications? A Systematic Review of Drug Interaction Data for Drugs Approved by the U.S. FDA in 2015 JF - Drug Metabolism and Disposition JO - Drug Metab Dispos DO - 10.1124/dmd.116.073411 SP - dmd.116.073411 AU - Jingjing Yu AU - Zhu Zhou AU - Katie H. Owens AU - Tasha K. Ritchie AU - Isabelle Ragueneau-Majlessi Y1 - 2016/01/01 UR - http://dmd.aspetjournals.org/content/early/2016/11/07/dmd.116.073411.abstract N2 - As a follow-up to previous reviews, the aim of the present analysis was to systematically examine all drug metabolism, transport, PK, and DDI data available in the 33 NDAs and 12 BLAs approved by the FDA in 2015, using the University of Washington Drug Interaction Database©, and to highlight the significant findings. All of the NDAs were well-characterized with regard to drug metabolism, transport, and/or organ impairment, and were fully analyzed in this review. In vitro, a majority of the NMEs were found to be substrates or inhibitors/inducers of at least one DME or transporter. In vivo, 95 clinical DDI studies displayed positive PK results with an AUC ratio ≥ 1.25 for inhibition or ≤ 0.8 for induction. When NMEs were considered as victim drugs, 21 NMEs had at least one positive clinical DDI, with three NMEs shown to be sensitive substrates of CYP3A (AUC ratio ≥ 5 when coadministered with strong inhibitors): cobimetinib, isavuconazole (the active metabolite of prodrug isavuconazonium sulfate), and ivabradine. As perpetrators, nine NMEs showed positive inhibition and three NMEs showed positive induction, some of these interactions involving both enzymes and transporters. The most significant changes for inhibition and induction were observed with rolapitant, a moderate inhibitor of CYP2D6 and lumacaftor, a strong inducer of CYP3A. PBPK simulations and PGx studies were used for six and eight NMEs, respectively, to inform dosing recommendations. The effects of hepatic or renal impairment on the drugs' PK were also evaluated to support drug administration in these specific populations. ER -