Metformin pharmacokinetics in nondiabetic pregnant women with polycystic ovary syndrome

Eur J Clin Pharmacol. 2011 Oct;67(10):1027-33. doi: 10.1007/s00228-011-1053-0. Epub 2011 May 3.

Abstract

Background: 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.

Objective: The objective of this study was to investigate the pharmacokinetics and the placental transfer of metformin in pregnant women with PCOS.

Patients and methods: 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.

Results: Metformin pharmacokinetic parameters were: t(½), 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).

Conclusion: 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.

MeSH terms

  • Adolescent
  • Adult
  • Female
  • Fetal Blood
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / blood
  • Hypoglycemic Agents / pharmacokinetics*
  • Hypoglycemic Agents / therapeutic use
  • Maternal-Fetal Exchange / drug effects
  • Metformin / adverse effects
  • Metformin / blood
  • Metformin / pharmacokinetics*
  • Metformin / therapeutic use
  • Polycystic Ovary Syndrome / drug therapy
  • Polycystic Ovary Syndrome / metabolism*
  • Pregnancy
  • Pregnancy Complications, Neoplastic / drug therapy
  • Pregnancy Complications, Neoplastic / metabolism*
  • Pregnancy Trimester, Third / drug effects
  • Young Adult

Substances

  • Hypoglycemic Agents
  • Metformin