DataSheet2_Selective Serotonin Reuptake Inhibitor Pharmacokinetics During Pregnancy: Clinical and Research Implications.xlsx

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.

妊娠及其相关的生理变化对众多药物，包括选择性5-羟色胺再摄取抑制剂——抑郁症和焦虑症的一线药理干预措施——的药代动力学产生影响。在妊娠期间，选择性5-羟色胺再摄取抑制剂（SSRI）表现出广泛的药代动力学变异性，这可能影响其耐受性和疗效。具体而言，与未孕女性相比，代谢SSRI的细胞色素P450（CYP）酶的活性发生剧烈变化（例如，CYP2C19活性降低，CYP2D6活性增加）。本视角探讨了与CYP活性相关的药代动力学基因在妊娠期间对SSRI药代动力学的影响。通过基于模拟的方法，考察了主要由CYP2C19（例如，艾司西酞普兰）和CYP2D6（例如，氟西汀）代谢的SSRI的血浆浓度，并讨论了其对于剂量调整和未来研究的意义。