Population pharmacokinetics of oseltamivir in non-pregnant and pregnant women

Venkateswaran C. Pillai, Kelong Han, Richard H. Beigi, Gary Hankins, Shannon Clark, Mary F. Hebert, Thomas R. Easterling, Anne Zajicek, Zhaoxia Ren, Steve N. Caritis, Raman Venkataramanan

    Research output: Contribution to journalArticle

    7 Citations (Scopus)

    Abstract

    Aims Physiological changes in pregnancy are expected to alter the pharmacokinetics of various drugs. The objective of this study was to evaluate systematically the pharmacokinetics of oseltamivir (OS), a drug used in the treatment of influenza during pregnancy. Methods A multicentre steady-state pharmacokinetic study of OS was performed in 35 non-pregnant and 29 pregnant women. Plasma concentration-time profiles were analyzed using both non-compartmental and population pharmacokinetic modelling (pop PK) and simulation approaches. A one compartment population pharmacokinetic model with first order absorption and elimination adequately described the pharmacokinetics of OS. Results The systemic exposure of oseltamivir carboxylate (OC, active metabolite of OS) was reduced approximately 30 (19-36)% (P <0.001) in pregnant women. Pregnancy significantly (P <0.001) influenced the clearance (CL/F) and volume of distribution (V/F) of OC. Both non-compartmental and population pharmacokinetic approaches documented approximately 45 (23-62)% increase in clearance (CL/F) of OC during pregnancy. Conclusion Based on the decrease in exposure of the active metabolite, the currently recommended doses of OS may need to be increased modestly in pregnant women in order to achieve comparable exposure with that of non-pregnant women.

    Original languageEnglish (US)
    Pages (from-to)1042-1050
    Number of pages9
    JournalBritish Journal of Clinical Pharmacology
    Volume80
    Issue number5
    DOIs
    StatePublished - Nov 1 2015

    Fingerprint

    Oseltamivir
    Pregnant Women
    Pharmacokinetics
    Population
    Pregnancy
    Pharmaceutical Preparations
    Human Influenza

    Keywords

    • oseltamivir
    • population pharmacokinetics
    • pregnancy

    ASJC Scopus subject areas

    • Pharmacology (medical)
    • Pharmacology

    Cite this

    Pillai, V. C., Han, K., Beigi, R. H., Hankins, G., Clark, S., Hebert, M. F., ... Venkataramanan, R. (2015). Population pharmacokinetics of oseltamivir in non-pregnant and pregnant women. British Journal of Clinical Pharmacology, 80(5), 1042-1050. https://doi.org/10.1111/bcp.12691

    Population pharmacokinetics of oseltamivir in non-pregnant and pregnant women. / Pillai, Venkateswaran C.; Han, Kelong; Beigi, Richard H.; Hankins, Gary; Clark, Shannon; Hebert, Mary F.; Easterling, Thomas R.; Zajicek, Anne; Ren, Zhaoxia; Caritis, Steve N.; Venkataramanan, Raman.

    In: British Journal of Clinical Pharmacology, Vol. 80, No. 5, 01.11.2015, p. 1042-1050.

    Research output: Contribution to journalArticle

    Pillai, VC, Han, K, Beigi, RH, Hankins, G, Clark, S, Hebert, MF, Easterling, TR, Zajicek, A, Ren, Z, Caritis, SN & Venkataramanan, R 2015, 'Population pharmacokinetics of oseltamivir in non-pregnant and pregnant women', British Journal of Clinical Pharmacology, vol. 80, no. 5, pp. 1042-1050. https://doi.org/10.1111/bcp.12691
    Pillai, Venkateswaran C. ; Han, Kelong ; Beigi, Richard H. ; Hankins, Gary ; Clark, Shannon ; Hebert, Mary F. ; Easterling, Thomas R. ; Zajicek, Anne ; Ren, Zhaoxia ; Caritis, Steve N. ; Venkataramanan, Raman. / Population pharmacokinetics of oseltamivir in non-pregnant and pregnant women. In: British Journal of Clinical Pharmacology. 2015 ; Vol. 80, No. 5. pp. 1042-1050.
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    AU - Hankins, Gary

    AU - Clark, Shannon

    AU - Hebert, Mary F.

    AU - Easterling, Thomas R.

    AU - Zajicek, Anne

    AU - Ren, Zhaoxia

    AU - Caritis, Steve N.

    AU - Venkataramanan, Raman

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    N2 - Aims Physiological changes in pregnancy are expected to alter the pharmacokinetics of various drugs. The objective of this study was to evaluate systematically the pharmacokinetics of oseltamivir (OS), a drug used in the treatment of influenza during pregnancy. Methods A multicentre steady-state pharmacokinetic study of OS was performed in 35 non-pregnant and 29 pregnant women. Plasma concentration-time profiles were analyzed using both non-compartmental and population pharmacokinetic modelling (pop PK) and simulation approaches. A one compartment population pharmacokinetic model with first order absorption and elimination adequately described the pharmacokinetics of OS. Results The systemic exposure of oseltamivir carboxylate (OC, active metabolite of OS) was reduced approximately 30 (19-36)% (P <0.001) in pregnant women. Pregnancy significantly (P <0.001) influenced the clearance (CL/F) and volume of distribution (V/F) of OC. Both non-compartmental and population pharmacokinetic approaches documented approximately 45 (23-62)% increase in clearance (CL/F) of OC during pregnancy. Conclusion Based on the decrease in exposure of the active metabolite, the currently recommended doses of OS may need to be increased modestly in pregnant women in order to achieve comparable exposure with that of non-pregnant women.

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