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Zhang, Nan; Shon, Jihong; Kim, Myong‐Jin; Yu, Chongwoo; Zhang, Lei; Huang, Shiew‐Mei; Lee, LaiMing; Tran, Doanh; Li, Li
Clinical and translational science, 20/May , Volume: 11, Issue: 3Journal Article
The general consensus is that CYP3A is the major enzyme for oxidative metabolism of EE and the commonly used progestins, including NET, LNG, NGM, and DRSP. ...most DDI studies assessing the effect of other drugs on the exposure of COCs have been conducted based on the possible interaction via CYP3A. In addition to CYP3A inhibition, atazanavir‐mediated inhibitory effect on UGT1A1 may contribute to this interaction. ...observation of more pronounced effects of atazanavir on the systemic exposure of NET may be explained by dual inhibition of CYP3A and UGT1A1. ...there has been no clinical evidence that ketoconazole or boceprevir inhibit other metabolic enzymes of DRSP, including reductases and sulfotransferases based on our literature search. ...contradictory to the in vitro data, the results of clinical DDI studies with strong CYP3A4 inhibitors ketoconazole and boceprevir indicated the contribution of CYP3A to the metabolism of DRSP. ...nuclear receptors pregnane X receptor and constitutive androstane receptor can mediate the regulation of some aldo‐keto reductase, which may play an important role in the biotransformation of NET, LNG, and DRSP. ...significant decrease in the exposure of EE and progestins in the presence of these inducers is likely attributed to induction on multiple metabolizing enzymes of steroid hormones including CYP3A, aldo‐keto reductase, UGT, and SULT.
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