title: Pharmacokinetics and diffusion into sputum of oseltamivir and oseltamivir carboxylate in adults with cystic fibrosis.
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.
authors.affiliation: Université Paris Descartes, Faculté de Médecine, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France. vincent.jullien@svp.aphp.fr
authors.forename: V
authors.initials: V
authors.lastname: Jullien
authors.forename: D
authors.initials: D
authors.lastname: Hubert
authors.forename: O
authors.initials: O
authors.lastname: Launay
authors.forename: G
authors.initials: G
authors.lastname: Babany
authors.forename: O
authors.initials: O
authors.lastname: Lortholary
authors.forename: I
authors.initials: I
authors.lastname: Sermet
mesh_terms: D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000493:pharmacokinetics*; D003550:Cystic Fibrosis / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D053139:Oseltamivir / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D013183:Sputum / Q000737:chemistry*; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D053139:Oseltamivir; C535162:oseltamivir carboxylate