A Study of the Pharmacology of Tamiflu in Pregnancy

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Study of the Pharmacology of Oseltamivir (Tamiflu-Roche) in Pregnancy

Conditions
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H1N1 Influenza Treatment During Pregnancy

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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) Exclusion Criteria: Unable to take medication orally Renal failure - creatinine > 1.5 Hct <28

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Tamiflu use during first trimester<br>This group will consist of twenty-five pregnant women who are being treated with Oseltamivir for clinical indications during the first trimester of their pregnancy. | |
| Tamiflu use during second trimester<br>This group will consist of twenty-five pregnant women who are being treated with Oseltamivir for clinical indications during the second trimester of their pregnancy. | |
| Tamiflu use during third trimester<br>This group will consist of twenty-five pregnant women who are being treated with Oseltamivir for clinical indications during the first trimester of their pregnancy. | |
| Tamiflu use in non-pregnant women<br>This group will consist of twenty-five non-pregnant healthy female volunteers who are being treated with Oseltamivir. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Apparent oral clearance of oseltamivir in singletons |  | At the time of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Concentration of oseltamivir carboxylate and oseltamivir at times 0 and 12h to ascertain steady state status |  | At the time of treatment | 
| Plasma esterase activity. (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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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H1N1 influenza, Swine flu, Oseltamivir, Tamiflu, Pregnancy