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Pharmacokinetics of oseltamivir among pregnant and nonpregnant women

https://doi.org/10.1016/j.ajog.2011.03.002Get rights and content

We sought to delineate the pharmacokinetics (PK) of oseltamivir and its active metabolite oseltamivir carboxylate during pregnancy. Physiologic changes of pregnancy, including increased renal filtration and secretion, may increase the clearance of oseltamivir carboxylate. Sixteen pregnant women taking oseltamivir for prophylaxis or treatment of suspected/proven influenza infection were enrolled. Twenty-three nonpregnant reproductive-age females served as the control group. The primary PK endpoint was area under the plasma concentration time curve for oseltamivir carboxylate. Pregnancy did not alter the PK parameters of the parent compound, oseltamivir. However, for oseltamivir carboxylate the area under the plasma concentration time curve was significantly lower (P = .007) and the apparent clearance significantly higher (P = .006) in pregnant women compared with nonpregnant women. Pregnancy produces lower systemic levels of oseltamivir carboxylate. Increasing the dose and/or dosing frequency of oseltamivir during pregnancy may be necessary to achieve comparable exposure in pregnant and nonpregnant women.

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Materials and methods

Women were recruited from 3 clinical research centers in the Eunice Kennedy Shriver National Institute of Child Health and Human Development–sponsored Obstetric-Fetal Pharmacology Research Units Network. Sites include Magee-Women's Hospital of the University of Pittsburgh Medical Center, Pittsburgh, PA; University of Texas Medical Branch, Galveston, TX; and the University of Washington Medical Center, Seattle, WA. Pregnant subjects were recruited and enrolled during the 2009 influenza season

Results

A total of 26 pregnant women were approached for participation, and 22 underwent the informed consent process. Six pregnant women opted for nonparticipation for various reasons after undergoing informed consent procedures. There were no nonpregnant women who underwent informed consent who subsequently decided not to participate. Data from 16 pregnant women and 23 nonpregnant control women were available for analysis.

The demographic characteristics for the 2 study populations are listed in Table

Comment

This study demonstrates that exposure to oseltamivir carboxylate (active metabolite of oseltamivir) following oral administration of oseltamivir is decreased by approximately 30% during pregnancy compared to nonpregnant women of reproductive age. While the precise clinical implications of these findings are not completely understood, this information is important and could have a substantial impact on dosing recommendations and antiviral effectiveness in pregnant women with influenza. The PK

Acknowledgment

The study team acknowledges Roche Pharmaceuticals for sample analysis and logistic support.

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    Conflict of Interest: This work was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (HD047905, HD047891, HD047892) and by the Office of Research on Women's Health, National Institutes of Health (NIH). Dr Mattison was supported by funds from the intramural program of NICHD, NIH. In addition, this work was supported in part by Grant no. UL1RR025014 from the NIH National Center for Research Resources. Drs Beigi, Han, Venkataramanan, Hankins, Clark, Hebert, Easterling, Zajicek, Ren, and Caritis have no conflicts to report.

    The contents of this article are the views of the authors and do not necessarily represent the official view of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Office of Research on Women's Health, or National Institutes of Health.

    Publication of this article was supported by the Centers for Disease Control and Prevention and the Association of Maternal and Child Health Programs.

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