title: Effect of type 2 diabetes mellitus on the pharmacokinetics of metformin in obese pregnant women.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Cláudia
authors.initials: C
authors.lastname: de Oliveira Baraldi
authors.forename: Elaine C D
authors.initials: EC
authors.lastname: Moisés
authors.forename: Teresa M
authors.initials: TM
authors.lastname: de Jesus Ponte Carvalho
authors.forename: Natalícia
authors.initials: N
authors.lastname: de Jesus Antunes
authors.forename: Vera L
authors.initials: VL
authors.lastname: Lanchote
authors.forename: Geraldo
authors.initials: G
authors.lastname: Duarte
authors.forename: Ricardo Carvalho
authors.initials: RC
authors.lastname: Cavalli
mesh_terms: D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000097:blood / Q000493:pharmacokinetics*; D008687:Metformin / Q000097:blood / Q000493:pharmacokinetics*; D009765:Obesity / Q000097:blood*; D011085:Polycystic Ovary Syndrome / Q000097:blood; D011247:Pregnancy / Q000097:blood*; D055815:Young Adult
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin