Clinical pharmacokinetics of laninamivir, a novel long-acting neuraminidase
inhibitor, after single and multiple inhaled doses of its prodrug, CS-8958, in
healthy male volunteers.
Author(s): Ishizuka H, Yoshiba S, Okabe H, Yoshihara K.
Affiliation(s): Translational Medicine and Clinical Pharmacology Department, Daiichi Sankyo Co,
Ltd, 1-2-58, Hiromachi, Shinagawa, Tokyo 140-8710, Japan.
ishizuka.hitoshi.h8@daiichisankyo.co.jp
Publication date & source: 2010, J Clin Pharmacol. , 50(11):1319-29
Phase 1 studies of laninamivir, a novel long-acting neuraminidase inhibitor, were
carried out to assess its safety, tolerability, and pharmacokinetics after
inhaled administration of its prodrug, CS-8958. Healthy male volunteers (total N
= 76) participated in double-blind, randomized, placebo-controlled trials and
received 5, 10, 20, 40, 80, or 120 mg of a single dose or 20 or 40 mg of a
twice-daily dose for 3 days. The clinical and laboratory parameters and plasma
and urinary concentrations of CS-8958 and laninamivir for 144 hours post dosing
were measured. There were no adverse events related to the test drug. CS-8958
disappeared from plasma with a half-life of about 2 hours, although laninamivir
was slowly eliminated from the body, lasting for even up to 144 hours after
administration with a half-life of about 3 days. Area under the curve and maximum
concentration increased almost linearly with the dose administered. The
cumulative urinary excretion amounts of CS-8958 and laninamivir were 2.3% to 3.6%
and 10.7% to 14.6% of the dose, respectively. The half-life of the urinary
excretion rates of laninamivir at higher single dose is comparable to plasma
half-life. CS-8958, when inhaled by healthy volunteers, is well tolerated and
exhibits a suitable pharmacokinetic profile, suggesting potential for
long-lasting anti-influenza activity.
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