title: An open-label crossover study to evaluate potential pharmacokinetic interactions between oral oseltamivir and intravenous zanamivir in healthy Thai adults.
abstract: There is no parenteral formulation of the neuraminidase inhibitor oseltamivir, the most widely used anti-influenza virus drug. Oseltamivir resistance is an increasing problem. Zanamivir is effective against the most prevalent oseltamivir-resistant influenza viruses. A parenteral formulation of zanamivir is in development for the treatment of severe influenza. It is not known if there is any pharmacokinetic interaction between the two drugs. Sixteen healthy Thai adult volunteers were studied in an open-label, four-period, randomized two-sequence crossover pharmacokinetic study in which zanamivir was given by constant-rate infusion or slow intravenous injection either alone or together with oral oseltamivir. Plasma concentration profiles of oseltamivir, the active metabolite oseltamivir carboxylate, and zanamivir were measured by liquid chromatography-mass spectrometry-mass spectrometry. Both drugs were well tolerated alone and in combination. The maximum plasma concentrations and the areas under the plasma concentration-time curves (AUC) of oseltamivir and oseltamivir carboxylate were not significantly different when oseltamivir was given separately or together with zanamivir. Maximum plasma concentrations of zanamivir were 10% (95% confidence interval, 7 to 12%) higher when zanamivir was infused concurrently with oral oseltamivir than with infusions before or after oral oseltamivir. The plasma zanamivir total AUC was positively correlated with the total oseltamivir carboxylate AUC (Pearson's correlation coefficient [r(P)] = 0.720, P = 0.002, n = 16) but not with the oseltamivir AUC (r(p) = 0.121, n = 16). There is no clinically significant pharmacokinetic interaction between oseltamivir and zanamivir.
authors.affiliation: Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Rd., Bangkok 10400, Thailand.
authors.forename: Sasithon
authors.initials: S
authors.lastname: Pukrittayakamee
authors.forename: Podjanee
authors.initials: P
authors.lastname: Jittamala
authors.forename: Kasia
authors.initials: K
authors.lastname: Stepniewska
authors.forename: Niklas
authors.initials: N
authors.lastname: Lindegardh
authors.forename: Sunee
authors.initials: S
authors.lastname: Chueasuwanchai
authors.forename: Wattana
authors.initials: W
authors.lastname: Leowattana
authors.forename: Aphiradee
authors.initials: A
authors.lastname: Phakdeeraj
authors.forename: Sutatip
authors.initials: S
authors.lastname: Permpunpanich
authors.forename: Warunee
authors.initials: W
authors.lastname: Hanpithakpong
authors.forename: Wirichada
authors.initials: W
authors.lastname: Pan-Ngum
authors.forename: Caroline
authors.initials: C
authors.lastname: Fukuda
authors.forename: Salwaluk
authors.initials: S
authors.lastname: Panapipat
authors.forename: Pratap
authors.initials: P
authors.lastname: Singhasivanon
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: White
authors.forename: Nicholas P J
authors.initials: NP
authors.lastname: Day
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000493:pharmacokinetics*; D044466:Asian People; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D053139:Oseltamivir / Q000493:pharmacokinetics*; D055815:Young Adult; D053243:Zanamivir / Q000493:pharmacokinetics*
chemical_list: D000998:Antiviral Agents; D053139:Oseltamivir; D053243:Zanamivir