A Study of the Pharmacology of Oseltamivir (Tamiflu-Roche) in Pregnancy
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 63
- 试验地点
- 4
- 主要终点
- Apparent oral clearance of oseltamivir in singletons
研究概览
简要总结
The purpose of this study is to determine the pharmacokinetics (PK) of the anti-flu medication, Tamiflu during pregnancy and to determine to what extent pregnancy may affect the currently recommended dosage of this medication.
详细描述
The emergence of the novel H1N1 influenza virus has raised concern among public health officials and the public alike. Although initial reports suggested that the risk of serious disease or death was less than initially feared, continued experience suggests that the disease will have a major impact on the public's health. To address this urgent public health challenge, the centers of the Obstetric-Fetal Pharmacology Research Units Network (OPRU) will recruit a total of 75 pregnant women (25 per trimester with singletons pregnancies) who are receiving oseltamivir for supposed influenza infection. When possible, we will recruit women with twin gestation to determine if fetal number affects the drugs pharmacokinetics. We do not anticipated a significant number of multi-fetal gestations (< 10) but even limited data might prove useful in this population given the tremendous change in renal drug clearance that is normally seen in this group of women. An additional 25 healthy non-pregnant women will be studied to define pregnancy- related changes in the PK of oseltamivir and the carboxylate.
We will study each woman once during therapy, performing steady state pharmacokinetic analyses. This study will be performed after 3 days of oral therapy to optimize the possibility that steady state concentrations have been achieved.
We will:
- collect biological fluids (plasma and urine) to further characterize the pharmacology of the drug;
- collect a check swab for DNA to allow study of the impact of single nucleotide polymorphisms on drug handing and disease expression;
- develop an assay or partner with others to develop an assay for oseltamivir and the primary metabolite, oseltamivir carboxylate;
- compare the pharmacokinetics of oseltamivir and its metabolite in each trimester of pregnancy to evaluate whether gestational age has an impact on the drug's pharmacokinetics;
- assess the impact of fetal number on the drug's pharmacokinetics;
- ask all participants about GI tolerance to the drug and any side effects they may be experiencing, especially related to mood and psychiatric well being; and
- on all pregnant subjects studied, when possible, we will obtain at delivery maternal and umbilical cord blood to evaluate placental transport especially in those who deliver proximate (within 3 days) to drug treatment.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
入排标准
- 年龄范围
- 14 Years 至 45 Years（Child, Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Taking or about to start oral oseltamivir for presumed influenza viral infection or for prophylaxis
- •Able to give informed consent
- •Pregnant female with singleton or multifetal gestation or healthy non-pregnant female (ancillary study)
排除标准
- •Unable to take medication orally
- •Renal failure - creatinine > 1.5
结局指标
主要结局
Apparent oral clearance of oseltamivir in singletons
时间窗: At the time of treatment
次要结局
- Plasma esterase activity. (ancillary study)(At the time of treatment)
- Apparent oral clearance of oseltamivir in twins(At the time of treatment)
- Apparent renal clearance of oseltamivir carboxylate in non-pregnant women (ancillary study)(At the time of treatment)
- Maternal side effects -GI upset, pregnancy loss, neuropsychiatric disorder(At the time of treatment)
- Maternal and cord blood oseltamivir and oseltamivir carboxylate concentrations(At delivery)
- Concentration of oseltamivir carboxylate and oseltamivir at times 0 and 12h to ascertain steady state status(At the time of treatment)