Poweleit Ethan A, Cinibulk Margaret A, Novotny Sarah A, Wagner-Schuman Melissa, Ramsey Laura B, Strawn Jeffrey R
Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.
Department of Biomedical Informatics, University of Cincinnati College of Medicine, Cincinnati, OH, United States.
Front Pharmacol. 2022 Feb 25;13:833217. doi: 10.3389/fphar.2022.833217. eCollection 2022.
Pregnancy and associated physiologic changes affect the pharmacokinetics of many medications, including selective serotonin reuptake inhibitors-the first-line pharmacologic interventions for depressive and anxiety disorders. During pregnancy, SSRIs exhibit extensive pharmacokinetic variability that may influence their tolerability and efficacy. Specifically, compared to non-pregnant women, the activity of cytochrome P450 (CYP) enzymes that metabolize SSRIs drastically changes (e.g., decreased CYP2C19 activity and increased CYP2D6 activity). This perspective examines the impact of pharmacokinetic genes-related to CYP activity on SSRI pharmacokinetics during pregnancy. Through a simulation-based approach, plasma concentrations for SSRIs metabolized primarily by CYP2C19 (e.g., escitalopram) and CYP2D6 (e.g., fluoxetine) are examined and the implications for dosing and future research are discussed.
怀孕及相关生理变化会影响许多药物的药代动力学，包括选择性5-羟色胺再摄取抑制剂（用于治疗抑郁和焦虑症的一线药物干预手段）。孕期，选择性5-羟色胺再摄取抑制剂表现出广泛的药代动力学变异性，这可能会影响其耐受性和疗效。具体而言，与未怀孕女性相比，代谢选择性5-羟色胺再摄取抑制剂的细胞色素P450（CYP）酶活性会发生显著变化（例如，CYP2C19活性降低，CYP2D6活性增加）。本文探讨了与CYP活性相关的药代动力学基因对孕期选择性5-羟色胺再摄取抑制剂药代动力学的影响。通过基于模拟的方法，研究了主要由CYP2C19（如艾司西酞普兰）和CYP2D6（如氟西汀）代谢的选择性5-羟色胺再摄取抑制剂的血浆浓度，并讨论了给药剂量的影响及未来研究方向。
