Pulmonary Pharmacokinetics of Oseltamivir Carboxylate in Rats after Nebulization or Intravenous Administration of Its Prodrug, Oseltamivir Phosphate

Abstract

The aim of this study was to investigate the pharmacokinetics of oseltamivir phosphate, a prodrug, and its active moiety in plasma and lung after its nebulization and intravenous administration in rats. Only 2% of prodrug was converted into active moiety presystematically, attesting to a low advantage of oseltamivir phosphate nebulization, suggesting that oseltamivir phosphate nebulization is not a good option to obtain a high exposure of the active moiety at the infection site within lung.

Keywords: lung; nebulization; oseltamivir; pharmacokinetics; prodrug.

FIG 1

Absorptive (apical to basolateral [AP/BL]) and secretory (basal to apical [BL/AP]) permeability (Papp) of OC (1 μg/ml) and OP (0.250 μg/ml) through Calu-3 cells (means ± the standard deviations, n = 3; *, P < 0.05, t test [Prism 5.02; GraphPad, La Jolla, CA]).

FIG 2

Experimental (means ± the standard deviations) and predicted concentration-time profiles of OP (A and C, left panel) and OC (B and D, right panel) after OP i.v administration (A and B, top panel) or NEB (C and D, bottom panel). Closed and open symbols represent concentrations measured in plasma and ELF, respectively. Solid lines represent predicted total plasma concentrations, dotted lines represent unbound plasma concentrations, and dashed lines represent predicted ELF concentrations.