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

NCT ID: NCT03710395

Last Updated: 2018-10-18

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-14
• Study Completion Date: 2019-10-01

Brief Summary

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.

Detailed 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.

Conditions

Drug Transporter

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Wild homozygous for ABCG2 c.421C>A

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

Group Type: ACTIVE_COMPARATOR

Blood and breast milk sampling

Intervention Type: PROCEDURE

At least 15 days after starting treatment with 20 mg slow-release nifedipine every 12 hours. Blood and breast milk will be sampled before first dosing in the morning.

Nifedipine

Intervention Type: DRUG

Chronic hypertensive breastfeeding women will be treated with slow-release 20 mg nifedipine, twice a day.

Variant genotypes for ABCG2 c.421C>A

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

Group Type: EXPERIMENTAL

Blood and breast milk sampling

Intervention Type: PROCEDURE

At least 15 days after starting treatment with 20 mg slow-release nifedipine every 12 hours. Blood and breast milk will be sampled before first dosing in the morning.

Nifedipine

Intervention Type: DRUG

Chronic hypertensive breastfeeding women will be treated with slow-release 20 mg nifedipine, twice a day.

Interventions

Blood and breast milk sampling

At least 15 days after starting treatment with 20 mg slow-release nifedipine every 12 hours. Blood and breast milk will be sampled before first dosing in the morning.

Intervention Type: PROCEDURE

Nifedipine

Chronic hypertensive breastfeeding women will be treated with slow-release 20 mg nifedipine, twice a day.

Intervention Type: DRUG

Other Intervention Names

Biological samples for nifedipine analysis; 20 mg nifedipine (slow-release)

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Hospital das Clínicas de Ribeirão Preto

OTHER

Sponsor Role: collaborator

Natalia Valadares de Moraes

OTHER

Sponsor Role: lead

Responsible Party

Natalia Valadares de Moraes

Professor of Toxicology

Responsibility Role: SPONSOR_INVESTIGATOR

Other Identifiers

NIFEDABCG2BCRP

Identifier Type: -

Identifier Source: org_study_id