Clinical Pharmacokinetics

, Volume 49, Issue 11, pp 741–765 | Cite as

Oseltamivir in Seasonal, Avian H5N1 and Pandemic 2009 A/H1N1 Influenza

Pharmacokinetic and Pharmacodynamic Characteristics
  • Nicolas Widmer
  • Pascal Meylan
  • Anton Ivanyuk
  • Manel Aouri
  • Laurent A. Decosterd
  • Thierry Buclin
Review Article


Oseltamivir is the ester-type prodrug of the neuraminidase inhibitor oseltamivir carboxylate. It has been shown to be an effective treatment for both seasonal influenza and the recent pandemic 2009 A/H1N1 influenza, reducing both the duration and severity of the illness. It is also effective when used preventively. This review aims to describe the current knowledge of the pharmacokinetic and pharmacodynamic characteristics of this agent, and to address the issue of possible therapeutic drug monitoring.

According to the currently available literature, the pharmacokinetics of oseltamivir carboxylate after oral administration of oseltamivir are characterized by mean ± SD bioavailability of 79 ± 12%, apparent clearance of 25.3±7.0L/h, an elimination half-life of 7.4±2.5 hours and an apparent terminal volume of distribution of 267 ± 122 L. A maximum plasma concentration of 342±83 μg/L, a time to reach the maximum plasma concentration of 4.2 ± 1.1 hours, a trough plasma concentration of 168±32mg/L and an area under the plasma concentration-time curve from 0 to 24 hours of 6110 ± 1330 mg · h/L for a 75 mg twice-daily regimen were derived from literature data. The apparent clearance is highly correlated with renal function, hence the dosage needs to be adjusted in proportion to the glomerular filtration rate. Interpatient variability is moderate (28% in apparent clearance and 46% in the apparent central volume of distribution); there is no indication of significant erratic or limited absorption in given patient subgroups.

The in vitro pharmacodynamics of oseltamivir carboxylate reveal wide variation in the concentration producing 50% inhibition of influenza A and B strains (range 0.17–44 μg/L). A formal correlation between systemic exposure to oseltamivir carboxylate and clinical antiviral activity or tolerance in influenza patients has not yet been demonstrated; thus no formal therapeutic or toxic range can be proposed.

The pharmacokinetic parameters of oseltamivir carboxylate after oseltamivir administration (bioavailability, apparent clearance and the volume of distribution) are fairly predictable in healthy subjects, with little interpatient variability outside the effect of renal function in all patients and bodyweight in children. Thus oseltamivir carboxylate exposure can probably be controlled with sufficient accuracy by thorough dosage adjustment according to patient characteristics. However, there is a lack of clinical study data on naturally infected patients. In addition, the therapeutic margin of oseltamivir carboxylate is poorly defined. The usefulness of systematic therapeutic drug monitoring in patients therefore appears to be questionable; however, studies are still needed to extend the knowledge to particular subgroups of patients or dosage regimens.



Support for this work was totally provided by internal funds. The authors have no conflicts of interest that are directly relevant to the content of this review. Marvin was used for drawing chemical structures and reactions (Marvin 5.3.7, 2010, Chemaxon []).


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Copyright information

© Adis Data Information BV 2010

Authors and Affiliations

  • Nicolas Widmer
    • 1
  • Pascal Meylan
    • 2
  • Anton Ivanyuk
    • 1
  • Manel Aouri
    • 1
  • Laurent A. Decosterd
    • 1
  • Thierry Buclin
    • 1
  1. 1.Division of Clinical Pharmacology and ToxicologyUniversity Hospital Center and University of LausanneLausanneSwitzerland
  2. 2.Microbiology InstituteUniversity Hospital Center and University of LausanneLausanneSwitzerland

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