Prodrug, laninamivir octanoate, a long-Acting neuraminidase inhibitor, using an easy-to-use inhaler in healthy volunteers

Abstract

Pharmacokinetic profiles of laninamivir after a single inhalation of laninamivir octanoate (LO), a prodrug of laninamivir, using a newly developed easy-to-use inhaler were evaluated in healthy volunteers. LO appeared rapidly in plasma after an inhaled administration in healthy volunteers with a median value of tmax of 0.25 hr, and the plasma concentrations decreased below the detection limit after 24 hr of inhalation. The median tmax of laninamivir was 4.0 hr and laninamivir slowly declined after Cmax with a mean t1/2 of 66.6 and 74.4 hr at a dose of 20 mg and 40 mg, respectively. The average AUC0-inf and Cmax for LO and laninamivir almost increased proportionally with the dose. The mean cumulative excretion amounts of LO in urine for 144 hr after inhaling 20 mg or 40 mg dose of LO were 4.7 and 5.5% of the dose, respectively, and those of laninamivir were 19.2 and 23.3%, respectively. No clinical or laboratory adverse experiences were reported and no subject discontinued because of an adverse experience. As plasma concentrations of both LO and laninamivir revealed a similar pattern between using the prototype and this new inhaler, LO exhibited potential for long lasting anti-influenza activity using this easy-to-use inhaler. © 2011 Yoshiba S, et al.