Department of Clinical Pharmacology, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway.
Department of Obstetrics and Gynecology, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway.
Basic Clin Pharmacol Toxicol. 2022 Mar;130(3):415-422. doi: 10.1111/bcpt.13703. Epub 2022 Jan 18.
Metformin is used to treat gestational diabetes. It is also used to treat women with polycystic ovary syndrome and has been shown to prevent late miscarriage and preterm birth. However, increased renal clearance during pregnancy causes a decline in serum concentrations of metformin. The aim of this study was to explore the time course of the pregnancy-related changes in metformin pharmacokinetics and the return to the non-pregnant state.
A subgroup of women in the PregMet2 study (n = 73) agreed to provide serum samples at three time-points in pregnancy (gestational weeks 19, 28 and 32) and once in post partum, (either 2, 4 or 8 weeks after delivery). Serum metformin concentrations were compared using a four-parameter logistic model.
The mean steady-state serum concentration of metformin during pregnancy was 9.39 μmoL/L, whereas the post partum concentration was 12.36 μmoL/L, an increase of 32% (p = 0,019). This change took place already during the first 2 weeks post partum.
Clinicians who treat pregnant women with metformin should be aware of the significant decrease in metformin concentration mediated by pregnancy, and the rapid increase after delivery, as it may impact both the therapeutic efficacy and the risk of adverse drug reactions.
二甲双胍用于治疗妊娠期糖尿病。它也用于治疗多囊卵巢综合征患者，并已被证明可预防晚期流产和早产。然而，怀孕期间肾脏清除率的增加导致血清二甲双胍浓度下降。本研究旨在探讨与妊娠相关的二甲双胍药代动力学变化的时间过程及其向非妊娠状态的恢复。
PregMet2 研究中的一部分女性（n = 73）同意在妊娠的三个时间点（妊娠 19、28 和 32 周）和产后（分娩后 2、4 或 8 周）提供血清样本。使用四参数逻辑模型比较血清二甲双胍浓度。
妊娠期间二甲双胍的平均稳态血清浓度为 9.39 μmol/L，而产后浓度为 12.36 μmol/L，增加了 32%（p = 0.019）。这种变化发生在产后的头 2 周内。
治疗妊娠妇女使用二甲双胍的临床医生应该意识到妊娠介导的二甲双胍浓度显著下降，以及产后的快速增加，因为这可能会影响治疗效果和不良反应的风险。
