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Effect of type 2 diabetes mellitus on the pharmacokinetics and transplacental transfer of nifedipine in hypertensive pregnant women
Author(s) -
Filgueira Gabriela Campos de Oliveira,
Filgueira Osmany Alberto Silva,
Carvalho Daniela Miarelli,
Marques Maria Paula,
Moisés Elaine Christine Dantas,
Duarte Geraldo,
Lanchote Vera Lucia,
Cavalli Ricardo Carvalho
Publication year - 2017
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.13226
Subject(s) - nifedipine , pharmacokinetics , medicine , volume of distribution , amniotic fluid , endocrinology , transplacental , fetus , pregnancy , pharmacology , placenta , calcium , biology , genetics
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.