Pharmacokinetics and diffusion into sputum of oseltamivir and oseltamivir carboxylate in adults with cystic fibrosis

Antimicrob Agents Chemother. 2011 Sep;55(9):4183-7. doi: 10.1128/AAC.00371-11. Epub 2011 Jun 13.

Abstract

Oseltamivir is a prodrug of oseltamivir carboxylate (OC), a neuraminidase inhibitor used for treatment and prevention of influenza. The pharmacokinetics of these 2 compounds were investigated after a single 75-mg oseltamivir dose in 6 patients with cystic fibrosis (CF). Means ± standard deviations of the area under the curve from time zero to infinity (AUC) were 173 ± 58 μg · h/liter for oseltamivir and 2,256 ± 394 μg · h/liter for OC. The concentrations of OC in sputum 4 to 6 h and 22 to 26 h after the intake ranged from 4.1 to 62.2 μg/liter. The AUC of OC was approximately 30% lower than and significantly different from published values for volunteers. On the basis of the present results and because the anti-A/H1N1 influenza virus efficacy of OC is related to its AUC/50% effective concentration (EC(50)) ratio, an increase in the oseltamivir unitary dose could be considered for the treatment of influenza in CF patients. This should nevertheless be confirmed by a controlled pharmacokinetic study performed on a larger number of patients.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antiviral Agents / pharmacokinetics*
  • Cystic Fibrosis / metabolism*
  • Female
  • Humans
  • Male
  • Oseltamivir / analogs & derivatives*
  • Oseltamivir / pharmacokinetics*
  • Sputum / chemistry*
  • Young Adult

Substances

  • Antiviral Agents
  • Oseltamivir
  • oseltamivir carboxylate