Article date: July 2017
By: Gabriela Campos de Oliveira Filgueira, Osmany Alberto Silva Filgueira, Daniela Miarelli Carvalho, Maria Paula Marques, Elaine Christine Dantas Moisés, Geraldo Duarte, Vera Lucia Lanchote, Ricardo Carvalho Cavalli in Volume 83, Issue 7, pages 1571-1579
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 (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: Cmax 23.52 ng ml−1, tmax 1.48 h, AUC0–12 202.23 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.
Conclusions
There was no influence of T2DM on the pharmacokinetics or placental transfer of nifedipine in hypertensive women with controlled diabetes.
DOI: 10.1111/bcp.13226
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