title: Effect of type 2 diabetes mellitus on the pharmacokinetics and transplacental transfer of nifedipine in hypertensive pregnant women.
abstract: Diabetes mellitus can inhibit cytochrome P450 3A4, an enzyme responsible for the metabolism of nifedipine, used for the treatment of hypertension in pregnant women. We aimed to assess the effect of type 2 diabetes mellitus (T2DM) on the pharmacokinetics, placental transfer and distribution of nifedipine in amniotic fluid in hypertensive pregnant women.
  
  
  
  The study was conducted in 12 hypertensive pregnant women [control group (CG)] and 10 hypertensive pregnant women with T2DM taking slow-release nifedipine (20 mg, 12/12 h). On the 34th week of gestation, serial blood samples were collected (0-12 h) after administration of the medication. At delivery, samples of maternal and fetal blood and amniotic fluid were collected for determination of nifedipine distribution in these compartments.
  
  
  
  The median pharmacokinetic parameters of CG were: peak plasma concentration (Cmax) 26.41 ng ml-1, time to reach Cmax(tmax) 1.79 h, area under the plasma concentration vs. time curve from 0-12 h (AUC0-12) 235.99 ng.h ml-1, half-life (t½) 4.34 h, volume of distribution divided by bioavailability (Vd/F) 560.96 l, and ClT/F 84.77 l h-1. The parameters for T2DM group were: Cmax23.52 ng ml-1, tmax1.48 h, AUC0-12202.23 ng.h ml-1, t½ 5.00 h, Vd/F 609.40 l, and apparent total clearance (ClT/F) 98.94 l h-1. The ratios of plasma concentrations of nifedipine in the umbilical vein, intervillous space and amniotic fluid to those in the maternal vein for CG and T2DM were 0.53 and 0.44, 0.78 and 0.87, respectively, with an amniotic fluid/maternal plasma ratio of 0.05 for both groups. The ratios of plasma concentrations in the umbilical artery to those in the umbilical vein were 0.82 for CG and 0.88 for T2DM.
  
  
  
  There was no influence of T2DM on the pharmacokinetics or placental transfer of nifedipine in hypertensive women with controlled diabetes.
authors.affiliation: Department of Obstetrics and Gynecology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Gabriela Campos de Oliveira
authors.initials: GCO
authors.lastname: Filgueira
authors.affiliation: Department of Obstetrics and Gynecology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Osmany Alberto Silva
authors.initials: OAS
authors.lastname: Filgueira
authors.affiliation: Department of Obstetrics and Gynecology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Daniela Miarelli
authors.initials: DM
authors.lastname: Carvalho
authors.affiliation: Department of Clinical, Toxicologic and Bromatologic Analyses, Faculty of Pharmaceutical Sciences of Ribeirão Pre, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Maria Paula
authors.initials: MP
authors.lastname: Marques
authors.affiliation: Department of Obstetrics and Gynecology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Elaine Christine Dantas
authors.initials: ECD
authors.lastname: Moisés
authors.affiliation: Department of Obstetrics and Gynecology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Geraldo
authors.initials: G
authors.lastname: Duarte
authors.affiliation: Department of Clinical, Toxicologic and Bromatologic Analyses, Faculty of Pharmaceutical Sciences of Ribeirão Pre, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Vera Lucia
authors.initials: VL
authors.lastname: Lanchote
authors.affiliation: Department of Obstetrics and Gynecology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Ricardo Carvalho
authors.initials: RC
authors.lastname: Cavalli
mesh_terms: D000328:Adult; D000653:Amniotic Fluid / Q000737:chemistry / Q000187:drug effects; D001682:Biological Availability; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016022:Case-Control Studies; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism*; D003692:Delayed-Action Preparations / Q000493:pharmacokinetics / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005260:Female; D006207:Half-Life; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D009543:Nifedipine / Q000493:pharmacokinetics* / Q000627:therapeutic use; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000188:drug therapy*
chemical_list: D002121:Calcium Channel Blockers; D003692:Delayed-Action Preparations; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D009543:Nifedipine
keywords: hypertension; pharmacokinetics; pregnancy; type 2 diabetes mellitus