Effect of pregnancy on the pharmacokinetics of metformin.
OBJECTIVE
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).


CONCLUSIONS
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.
Department of Clinical Pharmacology, Christchurch Hospital, Christchurch, New Zealand. ruth.hughes@xtra.co.nz
R C E
RC
Hughes
S J
SJ
Gardiner
E J
EJ
Begg
M
M
Zhang
D000328:Adult; D019540:Area Under Curve; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008687:Metformin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D049590:Postpartum Period; D011247:Pregnancy; D011263:Pregnancy Trimester, Third; D011254:Pregnancy in Diabetics / Q000188:drug therapy* / Q000378:metabolism
D007004:Hypoglycemic Agents; D008687:Metformin