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

Natalia Valadares de Moraes

Status and phase: Unknown; Phase 4

Conditions: Drug Transporter

Treatments: Procedure: Blood and breast milk sampling; Drug: Nifedipine

Study type: Interventional

Funder types: Other

Identifiers

NCT03710395

NIFEDABCG2BCRP

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 19 estimated patients

Sex: Female

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Chronic hypertensive breastfeeding women
• Patients being treated with 20 mg slow-release nifedipine every 12 hours for at least 15 days

Exclusion criteria

• Patients in use of ABCG2 inhibitors (omeprazole, pantoprazole, ritonavir, saquinavir, imatinib, efavirenz, nicardipine, abacavir, tacrolimus, ciclosporin A, cannabidiol);
• Patients who presented nifedipine adverse drug reactions
• Patients whose blood pressure normalized after delivery
• Patients who interrupted breastfeeding during the study
• Patients who did not return to the hospital for the clinical protocol.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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19 participants in 2 patient groups

Wild homozygous for ABCG2 c.421C>A

Active Comparator group

Description:

Chronic hypertensive breastfeeding women (18-45 years old) genotyped as wild homozygous for ABCG2 c.421C\>A.

Treatment:

Drug: Nifedipine

Procedure: Blood and breast milk sampling

Variant genotypes for ABCG2 c.421C>A

Experimental group

Description:

Chronic hypertensive breastfeeding women (18-45 years old) genotyped as heterozygous or mutant homozygous for ABCG2 c.421C\>A.

Treatment:

Drug: Nifedipine

Procedure: Blood and breast milk sampling