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

Drug Transporter Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03710395
• Other study ID #: NIFEDABCG2BCRP
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: December 14, 2015
• Est. completion date: October 1, 2019

Study information

• Verified date: October 2018
• Source: Universidade Estadual Paulista Júlio de Mesquita Filho
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 19
• Est. completion date: October 1, 2019
• Est. primary completion date: February 1, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

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.

Related Conditions & MeSH terms

• Drug Transporter

Intervention

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.

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

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Natalia Valadares de Moraes	Hospital das Clínicas de Ribeirão Preto

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Nifedipine concentration in plasma/milk ratio	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	Nifedipine concentration in plasma	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.
Secondary	Nifedipine concentration in milk	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.