Genetic Polymorphisms of ABCG2/BCRP on the Transport of Nifedipine to Breast Milk.
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Wild homozygous for ABCG2 c.421C>A Chronic hypertensive breastfeeding women (18-45 years old) genotyped as wild homozygous for ABCG2 c.421C>A. |
Procedure: 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.
Other Names:
Drug: Nifedipine
Chronic hypertensive breastfeeding women will be treated with slow-release 20 mg nifedipine, twice a day.
Other Names:
|
| Experimental: 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. |
Procedure: 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.
Other Names:
Drug: Nifedipine
Chronic hypertensive breastfeeding women will be treated with slow-release 20 mg nifedipine, twice a day.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Nifedipine concentration in plasma/milk ratio [After reaching steady state (at least 15 days of treatment), samples will be collected before first nifedipine dosing in the morning.]
The concentration ratio will be determined as (nifedipine concentration in plasma)/(nifedipine concentration in breast milk).
Secondary Outcome Measures
- Nifedipine concentration in plasma [After reaching steady state (at least 15 days of treatment), samples will be collected before first nifedipine dosing in the morning.]
The concentration of nifedipine in plasma determined by HPLC.
- Nifedipine concentration in milk [After reaching steady state (at least 15 days of treatment), samples will be collected before first nifedipine dosing in the morning.]
The concentration of nifedipine in breast milk determined by HPLC.
Eligibility Criteria
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.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Natalia Valadares de Moraes
- Hospital das Clínicas de Ribeirão Preto
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NIFEDABCG2BCRP