Influence of Genetic Polymorphisms of ABCG2/BCRP on the Transport of Nifedipine to Breast Milk in Hypertensive Breastfeeding Women.
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 19
- 主要终点
- Nifedipine concentration in plasma/milk ratio
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Chronic hypertensive breastfeeding women
- •Patients being treated with 20 mg slow-release nifedipine every 12 hours for at least 15 days
排除标准
- •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.
研究组 & 干预措施
Wild homozygous for ABCG2 c.421C>A
Chronic hypertensive breastfeeding women (18-45 years old) genotyped as wild homozygous for ABCG2 c.421C>A.
干预措施: Blood and breast milk sampling (Procedure)
Wild homozygous for ABCG2 c.421C>A
Chronic hypertensive breastfeeding women (18-45 years old) genotyped as wild homozygous for ABCG2 c.421C>A.
干预措施: Nifedipine (Drug)
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.
干预措施: Blood and breast milk sampling (Procedure)
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.
干预措施: Nifedipine (Drug)
结局指标
主要结局
Nifedipine concentration in plasma/milk ratio
时间窗: 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).
次要结局
- 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.)
- 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.)
研究者
Natalia Valadares de Moraes
Professor of Toxicology
Universidade Estadual Paulista Júlio de Mesquita Filho