Volume 23, Issue 3 pp. 323-326

Effect of pregnancy on the pharmacokinetics of metformin

R. C. E. Hughes

R. C. E. Hughes

Department of Clinical Pharmacology, Christchurch Hospital, Christchurch,

Department of Medicine, National Women's Hospital, Auckland and

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S. J. Gardiner

S. J. Gardiner

Department of Clinical Pharmacology, Christchurch Hospital, Christchurch,

Department of Medicine, Christchurch School of Medicine, Christchurch, New Zealand

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E. J. Begg

E. J. Begg

Department of Clinical Pharmacology, Christchurch Hospital, Christchurch,

Department of Medicine, Christchurch School of Medicine, Christchurch, New Zealand

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M. Zhang

M. Zhang

Department of Medicine, Christchurch School of Medicine, Christchurch, New Zealand

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First published: 16 February 2006
Citations: 42
Dr Ruth Hughes, Department of Clinical Pharmacology, Christchurch Hospital, Private Bag 4710, Christchurch, New Zealand. E-mail: [email protected]

Abstract

Aims  To determine the effects of pregnancy on metformin pharmacokinetics.

Methods  Seven women with Type 2 diabetes mellitus taking metformin throughout pregnancy were studied on two occasions, once at 28–36 weeks gestation and once at least 8 weeks postpartum. Serum metformin concentrations were determined across a dosing interval using high-performance liquid chromatography. The areas under the serum concentration-time curve from 0 to 4 h post-dose (AUC0−4) and 0 to 8 h post-dose (AUC0−8) where possible, were compared in the pregnant and non-pregnant state.

Results  Metformin concentrations were lower in pregnancy in six subjects, with a mean (95% CI) AUC0−4 that was 69% (53.6, 84.8) of the postpartum value. The AUC0−4 of one subject was higher in pregnancy at 142% of the postpartum value. Overall, the mean (95% CI) AUC0−4 during pregnancy for all seven subjects was 80% (51.3, 107.8) of the postpartum value (P = 0.053, two-tailed t-test; P = 0.027, one-tailed t-test).

Conclusion  These results are consistent with our hypothesis that the clearance of metformin increases in pregnancy as a result of enhanced renal elimination. A larger study is required to establish whether metformin dose adjustments are required in late pregnancy to maintain therapeutic effect.

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