Genetic Polymorphisms of ABCG2/BCRP on the Transport of Nifedipine to Breast Milk.

Overview

This study aims to investigate the influence of the c.421C\>A genetic polymorphism of the ABCG2 / BCRP transporter in the concentration ratio of nifedipine in maternal milk:plasma in hypertensive breastfeeding women attended at the Gynecology and Obstetrics Service of the Medical School of Ribeirão Preto, of the University of São Paulo. Thus, plasma and breast milk samples are being collected from patients in chronic use of the drug (n=30) within 15 to 30 days postnatal.

The breast cancer resistance protein (ABCG2/BCRP) human transporter, encoded by the ABCG2 gene, is highly expressed on the human lactating breast. Nifedipine, a known substrate of ABCG2, is used for the treatment of hypertension in pregnancy and during breastfeeding. ABCG2 plays an important role on secreting drugs and xenobiotics into milk. The aim of the present study was to evaluate the effect of ABCG2 c.421C\>A on nifedipine breast milk/plasma concentration ratio in hypertensive breastfeeding women. Nineteen hypertensive breastfeeding women treated with 20 mg slow-release nifedipine every 12 hours were investigated. Blood and breast milk samples were collected simultaneously 15-30 days after delivery and at least 15 days after drug treatment, in order to reach drug steady state. All patients were genotyped for ABCG2 c.421C\>A using real time-PCR. Nifedipine concentration was determined in plasma and breast milk by high-performance liquid chromatography using UV detection. The comprehension of the variability in the transport of nifedipine to breast milk in hypertensive breastfeeding women will contribute to the evaluation of drug exposure in breast-fed infants to nifedipine and other ABCG2 substrates.

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