title: Metformin pharmacokinetics in nondiabetic pregnant women with polycystic ovary syndrome.
abstract: BACKGROUND
  The use of metformin throughout gestation by pregnant women with polycystic ovary syndrome (PCOS) significantly reduces the number of first trimester spontaneous abortions and the rate of occurrence of gestational diabetes.
  
  
  OBJECTIVE
  The objective of this study was to investigate the pharmacokinetics and the placental transfer of metformin in pregnant women with PCOS.
  
  
  METHODS
  Eight pregnant women with PCOS taking 850 mg metformin every 12 h during the third trimester of pregnancy were evaluated. Maternal blood samples were collected at steady state during the dose interval (0-12 h). Maternal and umbilical cord blood samples were also obtained at delivery. Metformin plasma concentrations were analyzed by high-performance liquid chromatography, and pharmacokinetic parameters were determined using a non-compartmental model. Data are reported as median and minimum and maximum values.
  
  
  RESULTS
  Metformin pharmacokinetic parameters were: t(½), 3.8 (2.8-5.4) h; t(max), 2.0 (0.5-3.0) h; C(max), 1.4 (0.5-2.1) mg/L; C(mean), 0.5 (0.2-0.9) mg/L; AUC(0-12), 6.4 (1.1-9.2) mg h/L; Cl/f, 105 (60-274) L/h; Vd/f, 551 (385-1173) L; median fluctuation, 89 (79-95)%. Umbilical/maternal metformin plasma concentration ratios were 0.7 (0.4-1.3).
  
  
  CONCLUSIONS
  Metformin oral clearance (Cl/f) had increased in our patients relative to nonpregnant healthy volunteers or diabetic patients. Therefore, lower plasma metformin concentrations were observed for nondiabetic pregnant women with PCOS. Future studies should be conducted to demonstrate the therapeutic efficacy of metformin during pregnancy. Caution is warranted as umbilical/maternal metformin plasma concentrations ratios of around 0.7 require metformin dosage adjustment.
authors.affiliation: Department of Gynecology and Obstetrics, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.
authors.forename: Cláudia
authors.initials: C
authors.lastname: de Oliveira Baraldi
authors.forename: Vera Lucia
authors.initials: VL
authors.lastname: Lanchote
authors.forename: Natalícia
authors.initials: N
authors.lastname: de Jesus Antunes
authors.forename: Teresa Maria
authors.initials: TM
authors.lastname: de Jesus Ponte Carvalho
authors.forename: Elaine Christine
authors.initials: EC
authors.lastname: Dantas Moisés
authors.forename: Elaine Christine
authors.initials: EC
authors.lastname: Dantes Moisés
authors.forename: Geraldo
authors.initials: G
authors.lastname: Duarte
authors.forename: Ricardo Carvalho
authors.initials: RC
authors.lastname: Cavalli
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D005312:Fetal Blood; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008431:Maternal-Fetal Exchange / Q000187:drug effects; D008687:Metformin / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy / Q000378:metabolism*; D011247:Pregnancy; D011252:Pregnancy Complications, Neoplastic / Q000188:drug therapy / Q000378:metabolism*; D011263:Pregnancy Trimester, Third / Q000187:drug effects; D055815:Young Adult
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin