Population pharmacokinetics of metformin in late pregnancy

Charles, B., Norris, R., Xiao, X. N. and Hague, W. (2006) Population pharmacokinetics of metformin in late pregnancy. Therapeutic Drug Monitoring, 28 1: 67-72. doi:10.1097/01.ftd.0000184161.52573.0e

Author Charles, B.
Norris, R.
Xiao, X. N.
Hague, W.
Title Population pharmacokinetics of metformin in late pregnancy
Journal name Therapeutic Drug Monitoring   Check publisher's open access policy
ISSN 0163-4356
Publication date 2006
Sub-type Article (original research)
DOI 10.1097/01.ftd.0000184161.52573.0e
Volume 28
Issue 1
Start page 67
End page 72
Total pages 6
Editor G. Koren
M. Oellerich
Place of publication USA
Publisher Lippincott Williams & Wilkins
Collection year 2006
Language eng
Subject C1
320503 Clinical Pharmacology and Therapeutics
730105 Endocrine organs and diseases (incl. diabetes)
Abstract The pharmacokinetic disposition of metformin in late pregnancy was studied together with the level of fetal exposure at birth. Blood samples were obtained in the third trimester of pregnancy from women with gestational diabetes or type 2 diabetes, 5 had a previous diagnosis of polycystic ovary syndrome. A cord blood sample also was obtained at the delivery of some of these women, and also at delivery of others who had been taking metformin during pregnancy but from whom no blood had been taken. Plasma metformin concentrations were assayed by a new, validated, reverse-phase HPLC method, A 2-compartment, extravascular maternal model with transplacental partitioning of drug to a fetal compartment was fitted to the data. Nonlinear mixed-effects modeling was performed in'NONMEM using FOCE with INTERACTION. Variability was estimated using logarithmic interindividual and additive residual variance models; the covariance between clearance and volume was modeled simultaneously. Mean (range) metformin concentrations in cord plasma and in maternal plasma were 0.81 (range, 0.1-2.6) mg/L and 1.2 (range, 0. 1-2.9) mg/L, respectively. Typical population values (interindividual variability, CV%) for allometrically scaled maternal clearance and volume of distribution were 28 L/h/70 kg (17.1%) and 190 L/70 ka (46.3%), giving a derived population-wide half-life of 5.1 hours. The placental partition coefficient for metformin was 1.07 (36.3%). Neither maternal age nor weight significantly influenced the pharmacokinetics. The variability (SD) of observed concentrations about model-predicted concentrations was 0.32 mg/L. The pharmacokinetics were similar to those in nonpregnant patients and, therefore, no dosage adjustment is warranted. Metformin readily crosses the placenta, exposing the fetus to concentrations approaching those in the maternal circulation. The sequelae to such exposure, ea, effects on neonatal obesity and insulin resistance, remain unknown.
Keyword Medical Laboratory Technology
Pharmacology & Pharmacy
Population Pharmacokinetics
Fetal Exposure
Therapeutic Drug Monitoring
Drug Transfer
Human Placenta
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
2007 Higher Education Research Data Collection
School of Pharmacy Publications
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Citation counts: TR Web of Science Citation Count  Cited 48 times in Thomson Reuters Web of Science Article | Citations
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Created: Wed, 15 Aug 2007, 06:55:15 EST