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Effect of Type 2 Diabetes Mellitus on the Pharmacokinetics of Metformin in Obese Pregnant Women

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Abstract

Background and Objective

The use of metformin throughout gestation by women with polycystic ovary syndrome (PCOS) and type 2 diabetes mellitus (T2DM) significantly reduces the number of first-trimester spontaneous abortions and the rate of occurrence of gestational diabetes and hypertensive syndromes. Metformin is taken up into renal tubular cells by organic cation transport 2 (OCT2) and eliminated unchanged into the urine. The objective of this study was to analyse the influence of T2DM on the pharmacokinetics of metformin in obese pregnant women and in a control group of non-diabetic obese pregnant women with PCOS.

Methods

Eight non-diabetic obese pregnant women with PCOS and nine obese pregnant women with T2DM taking oral metformin 850 mg every 12 h were evaluated throughout gestation. Serial blood samples were collected over a 12-h period during the third trimester of pregnancy. Steady-state plasma concentrations of metformin were determined by high-performance liquid chromatography with a UV detector. The pharmacokinetic results of the two groups, reported as median and 25th and 75th percentile, were compared statistically using the Mann–Whitney test, with the level of significance set at p < 0.05.

Results

The pharmacokinetic parameters detected for PCOS versus T2DM patients, reported as median, were, respectively: elimination half-life 3.75 versus 4.00 h; time to maximum concentration 2.00 versus 3.00 h; maximum concentration 1.42 versus 1.21 μg/mL; mean concentration 0.53 versus 0.56 μg/mL; area under the plasma concentration–time curve from time zero to 12 h 6.42 versus 6.73 μg·h/mL; apparent total oral clearance 105.39 versus 98.38 L/h; apparent volume of distribution after oral administration 550.51 versus 490.98 L; and fluctuation (maximum–minimum concentration variation) of 179.56 versus 181.73 %. No significant differences in pharmacokinetic parameters were observed between the groups.

Conclusion

T2DM in the presence of insulin use does not influence the pharmacokinetics of metformin in pregnant patients, demonstrating the absence of a need to increase the dose, and consequently does not influence the OCT2-mediated transport in pregnant women with PCOS.

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Acknowledgments

The authors have no conflicts of interest that are directly relevant to the content of this study. This article is part of a line of research that has received funding from the Foundation for Research Support of São Paulo (FAPESP) and National Council for Scientific and Technological Development (CNPq), Brazil.

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Authors and Affiliations

  1. Department of Gynecology and Obstetrics, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Av Bandeirantes 3900, Campus da USP, CEP 14049-900, Ribeirão Preto, Brazil

    Cláudia de Oliveira Baraldi, Elaine C. D. Moisés, Geraldo Duarte & Ricardo Carvalho Cavalli

  2. Department of Clinical, Toxicologic and Bromatologic Analyses, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil

    Teresa M. de Jesus Ponte Carvalho, Natalícia de Jesus Antunes & Vera L. Lanchote

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  1. Cláudia de Oliveira Baraldi
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  2. Elaine C. D. Moisés
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  4. Natalícia de Jesus Antunes
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Correspondence to Ricardo Carvalho Cavalli.

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de Oliveira Baraldi, C., Moisés, E.C.D., de Jesus Ponte Carvalho, T.M. et al. Effect of Type 2 Diabetes Mellitus on the Pharmacokinetics of Metformin in Obese Pregnant Women. Clin Pharmacokinet 51, 743–749 (2012). https://doi.org/10.1007/s40262-012-0008-7

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