Major depressive disorder (MDD) is a common disorder in pregnancy. Although sertraline is the most frequently prescribed antidepressant for pregnant people in the United States, limited information about its pharmacokinetics in pregnancy is available. Our objectives were to characterize plasma sertraline concentration to dose (C/D) ratios across pregnancy and postpartum and investigate the effect of pharmacogenetic variability on sertraline elimination. We performed a prospective observational cohort study in people with a singleton pregnancy ≤ 18 weeks gestation and a lifetime diagnosis of MDD at the 3 Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)-funded Obstetrical-Fetal Pharmacology Research Center sites. Subjects (N = 47) were receiving maintenance sertraline therapy and chose to continue it during pregnancy. Blood samples were obtained 24-hours postdose every 4 weeks across pregnancy and twice postpartum for measurement of plasma concentrations of sertraline and desmethylsertraline. Overall mean sertraline C/D ratios were decreased at study onset and remained consistently low until after delivery. During the last 4 weeks of pregnancy the mean sertraline C/D ratio (95% confidence interval (CI)), 0.25 (95% CI, 0.19, 0.3) ng/mL/dose (mg/day), was smaller than the mean ratio at ≥ 8 weeks after delivery, 0.32 (95% CI, 0.27, 0.37) ng/mL/dose (mg/day), a 22% difference. Mean sertraline/desmethylsertraline ratios were highest after birth, which confirmed increased sertraline elimination during pregnancy. Sertraline C/D ratios in participants with functional CYP2C19 activity did not change significantly during pregnancy, whereas ratios in participants with poor or intermediate CYP2C19 activity decreased by 51%. Exploratory pharmacogenomic analysis indicated that pregnant people with poor or intermediate CYP2C19 activity are at risk for subtherapeutic sertraline concentrations during pregnancy.

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妊娠期和产后舍曲林血浆浓度的变化

重度抑郁症 (MDD) 是妊娠期常见的疾病。尽管舍曲林是美国孕妇最常用的抗抑郁药，但有关其在妊娠期药代动力学的信息有限。我们的目标是描述妊娠期和产后血浆舍曲林浓度与剂量 (C/D) 比率的特征，并研究药物遗传学变异性对舍曲林消除的影响。我们在 3 Eunice Kennedy Shriver 国立儿童健康与人类发展研究所 (NICHD) 资助的产科-胎儿药理学研究中心开展了一项前瞻性观察性队列研究，对象是单胎妊娠≤ 18 周且终身诊断为 MDD 的人。科目 ( N = 47) 正在接受舍曲林维持治疗并选择在怀孕期间继续治疗。妊娠期间每 4 周在给药后 24 小时采集血样，产后采集两次血样，用于测量舍曲林和去甲基舍曲林的血浆浓度。总体平均舍曲林 C/D 比率在研究开始时降低，并一直保持在分娩后的低水平。在妊娠的最后 4 周期间，平均舍曲林 C/D 比率（95% 置信区间 (CI)）为 0.25（95% CI，0.19、0.3）ng/mL/剂量（mg/天），小于平均值分娩后 ≥ 8 周时的比率为 0.32（95% CI，0.27，0.37）ng/mL/剂量（mg/天），差异为 22%。平均舍曲林/去甲基舍曲林比率在出生后最高，这证实了怀孕期间舍曲林消除增加。具有功能性 CYP2C19 活性的参与者的舍曲林 C/D 比率在怀孕期间没有显着变化，而具有低或中等 CYP2C19 活性的参与者的比率下降了 51%。探索性药物基因组学分析表明，CYP2C19 活性较差或处于中等水平的孕妇在怀孕期间存在舍曲林浓度低于治疗剂量的风险。