DRUGS IN PREGNANCY AND LACTATION Effect of type 2 diabetes mellitus on the pharmacokinetics and transplacental transfer of nifedipine in hypertensive pregnant women Correspondence Ricardo Carvalho Cavalli, Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, Departamento de Ginecologia e Obstetrícia FMRP-USP, 8° andar, Avenida Bandeirantes, 3900, Campus da USP, Ribeirão Preto, SP 14049-900, Brazil. Tel.: +55 16 3602 2804; Fax: +55 16 3633 0946; E-mail: rcavalli@fmrp.usp.br Received 1 August 2016; Revised 15 December 2016; Accepted 22 December 2016 Gabriela Campos de Oliveira Filgueira 1 , Osmany Alberto Silva Filgueira 1 , Daniela Miarelli Carvalho 1 , Maria Paula Marques 2 , Elaine Christine Dantas Moisés 1 , Geraldo Duarte 1 , Vera Lucia Lanchote 2 and Ricardo Carvalho Cavalli 1 1 Department of Obstetrics and Gynecology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil, and 2 Department of Clinical, Toxicologic and Bromatologic Analyses, Faculty of Pharmaceutical Sciences of Ribeirão Pre, University of São Paulo, Ribeirão Preto, São Paulo, Brazil Keywords hypertension, pharmacokinetics, pregnancy, type 2 diabetes mellitus AIMS 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. METHODS 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. RESULTS The median pharmacokinetic parameters of CG were: peak plasma concentration (C max ) 26.41 ng ml 1 , time to reach C max (t max ) 1.79 h, area under the plasma concentration vs. time curve from 0–12 h (AUC 0–12 ) 235.99 ng.h ml 1 , half-life (t½) 4.34 h, volume of distribution divided by bioavailability (Vd/F) 560.96 l, and Cl T /F 84.77 l h 1 . The parameters for T2DM group were: C max 23.52 ng ml 1 ,t max 1.48 h, AUC 0–12 202.23 ng.h ml 1 , t½ 5.00 h, Vd/F 609.40 l, and apparent total clearance (Cl T /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. CONCLUSIONS There was no influence of T2DM on the pharmacokinetics or placental transfer of nifedipine in hypertensive women with controlled diabetes. British Journal of Clinical Pharmacology Br J Clin Pharmacol (2017) 83 1571–1579 1571 © 2017 The British Pharmacological Society DOI:10.1111/bcp.13226