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

October 15, 2018 updated by: Natalia Valadares de Moraes

Influence of Genetic Polymorphisms of ABCG2/BCRP on the Transport of Nifedipine to Breast Milk in Hypertensive Breastfeeding Women.

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

19

Phase

  • Phase 4

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 45 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Female

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / 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:
  • Biological samples for nifedipine analysis
Drug: Nifedipine
Chronic hypertensive breastfeeding women will be treated with slow-release 20 mg nifedipine, twice a day.
Other Names:
  • 20 mg nifedipine (slow-release)
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:
  • Biological samples for nifedipine analysis
Drug: Nifedipine
Chronic hypertensive breastfeeding women will be treated with slow-release 20 mg nifedipine, twice a day.
Other Names:
  • 20 mg nifedipine (slow-release)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Nifedipine concentration in plasma/milk ratio
Time Frame: 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).
After reaching steady state (at least 15 days of treatment), samples will be collected before first nifedipine dosing in the morning.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Nifedipine concentration in plasma
Time Frame: 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.
After reaching steady state (at least 15 days of treatment), samples will be collected before first nifedipine dosing in the morning.
Nifedipine concentration in milk
Time Frame: 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.
After reaching steady state (at least 15 days of treatment), samples will be collected before first nifedipine dosing in the morning.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Natalia Valadares de Moraes

Collaborators

Hospital das Clínicas de Ribeirão Preto

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

December 14, 2015

Primary Completion (ACTUAL)

February 1, 2018

Study Completion (ANTICIPATED)

October 1, 2019

Study Registration Dates

First Submitted

July 17, 2018

First Submitted That Met QC Criteria

October 15, 2018

First Posted (ACTUAL)

October 18, 2018

Study Record Updates

Last Update Posted (ACTUAL)

October 18, 2018

Last Update Submitted That Met QC Criteria

October 15, 2018

Last Verified

October 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NIFEDABCG2BCRP

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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