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: t½, 3.8 (2.8–5.4) h; tmax, 2.0 (0.5–3.0) h; Cmax, 1.4 (0.5–2.1) mg/L; Cmean, 0.5 (0.2–0.9) mg/L; AUC0–12, 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.
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Acknowledgments
The authors are grateful to Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Fundação de Apoio a Pesquisa e Assistência do HCFMRP-USP (FAEPA) and to Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) for financial support and for granting research fellowships.
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An erratum to this article can be found at http://dx.doi.org/10.1007/s00228-011-1116-2
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de Oliveira Baraldi, C., Lanchote, V.L., de Jesus Antunes, N. et al. Metformin pharmacokinetics in nondiabetic pregnant women with polycystic ovary syndrome. Eur J Clin Pharmacol 67, 1027–1033 (2011). https://doi.org/10.1007/s00228-011-1053-0
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DOI: https://doi.org/10.1007/s00228-011-1053-0