A Study of the Pharmacology of Tamiflu in Pregnancy
Condition: H1N1 Influenza Treatment During Pregnancy
MeSH terms: Influenza, Human
Study type: Observational

Summary: 
      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: 
      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:

        1. collect biological fluids (plasma and urine) to further characterize the pharmacology of
           the drug;

        2. collect a check swab for DNA to allow study of the impact of single nucleotide
           polymorphisms on drug handing and disease expression;

        3. develop an assay or partner with others to develop an assay for oseltamivir and the
           primary metabolite, oseltamivir carboxylate;

        4. 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;

        5. assess the impact of fetal number on the drug's pharmacokinetics;

        6. 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

        7. 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.
    

Observational model: Cohort
Sampling method: Non-Probability Sample
Study population: 
        Pregnant and non-pregnant women
      
Biospecimen description: 
      Blood and urine
    
Keywords: H1N1 influenza; Swine flu; Oseltamivir; Tamiflu; Pregnancy