Metformin pharmacokinetics in nondiabetic pregnant women with polycystic ovary syndrome
Metformin pharmacokinetics in nondiabetic pregnant women with polycystic ovary syndrome
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DOI：
10.1007/s00228-011-1053-0
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发表时间：
2011-10-01
影响因子：
2.9
通讯作者：
Cavalli, Ricardo Carvalho
中科院分区：
文献类型：
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作者：
Baraldi, Claudia de Oliveira;Lanchote, Vera Lucia;Cavalli, Ricardo Carvalho
多囊卵巢综合征（PCOS）孕妇在整个妊娠期使用二甲双胍本研究旨在探讨二甲双胍在多囊卵巢综合征（PCOS）孕妇中的药代动力学及胎盘转运情况，对8例PCOS孕妇在孕晚期服用二甲双胍850 mg，每12 h一次，观察其在PCOS孕妇中的药代动力学及胎盘转运情况。妊娠的评估。在给药间隔（0-12 h）内采集稳态母体血样。分娩时还采集了母体和脐带血样本。通过高效液相色谱法分析二甲双胍血浆浓度，并使用非房室模型确定药代动力学参数。数据以中位数、最小值和最大值报告，代谢动力学参数为：t（A1/2），3.8（2.8-5.4）h; t（max），2.0（0.5-3.0）h; C-max，1.4（0.5-2.1）mg/L; C均值，0.5（0.2-0.9）mg/L; AUC（0-12），6.4（1.1-9.2）mg h/L; Cl/f，105（60-274）L/h; Vd/f，551（385-1173）L;中位波动，89（79-95）%。孕妇/母体二甲双胍血药浓度比为0.7（0.4-1.3）。相对于非妊娠健康志愿者或糖尿病患者，我们患者的二甲双胍口服清除率（Cl/f）增加。因此，在非糖尿病PCOS孕妇中观察到较低的二甲双胍血浆浓度。应进行进一步研究以证明妊娠期间二甲双胍的治疗疗效。由于脐带/母体二甲双胍血药浓度比约为0.7，需要调整二甲双胍剂量，因此需要谨慎。
The use of metformin throughout gestation by pregnant women with polycystic ovary syndrome (PCOS) significantly reduces the number of first trimester spontaneous abortions and the rate of occurrence of gestational diabetes.The objective of this study was to investigate the pharmacokinetics and the placental transfer of metformin in pregnant women with PCOS.Eight pregnant women with PCOS taking 850 mg metformin every 12 h during the third trimester of pregnancy were evaluated. Maternal blood samples were collected at steady state during the dose interval (0-12 h). Maternal and umbilical cord blood samples were also obtained at delivery. Metformin plasma concentrations were analyzed by high-performance liquid chromatography, and pharmacokinetic parameters were determined using a non-compartmental model. Data are reported as median and minimum and maximum values.Metformin pharmacokinetic parameters were: t(A1/2), 3.8 (2.8-5.4) h; t(max), 2.0 (0.5-3.0) h; C-max, 1.4 (0.5-2.1) mg/L; C-mean, 0.5 (0.2-0.9) mg/L; AUC(0-12), 6.4 (1.1-9.2) mg h/L; Cl/f, 105 (60-274) L/h; Vd/f, 551 (385-1173) L; median fluctuation, 89 (79-95)%. Umbilical/maternal metformin plasma concentration ratios were 0.7 (0.4-1.3).Metformin oral clearance (Cl/f) had increased in our patients relative to nonpregnant healthy volunteers or diabetic patients. Therefore, lower plasma metformin concentrations were observed for nondiabetic pregnant women with PCOS. Future studies should be conducted to demonstrate the therapeutic efficacy of metformin during pregnancy. Caution is warranted as umbilical/maternal metformin plasma concentrations ratios of around 0.7 require metformin dosage adjustment.