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.

Abstract

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.

• Authors: Hitoshi Ishizuka, Satoshi Yoshiba, Hiromi Okabe, Kazutaka Yoshihara
• Journal: Journal of clinical pharmacology (J Clin Pharmacol) Vol. 50 Issue 11 Pg. 1319-29 (Nov 2010) ISSN: 1552-4604 [Electronic] England
• PMID: 20145259 (Publication Type: Clinical Trial, Phase I, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• CS 8958
• Enzyme Inhibitors
• Guanidines
• Prodrugs
• Pyrans
• Sialic Acids
• laninamivir
• Neuraminidase
• Zanamivir

Topics

• Administration, Inhalation
• Adult
• Area Under Curve
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug Administration Schedule
• Enzyme Inhibitors (adverse effects, pharmacokinetics)
• Guanidines
• Half-Life
• Humans
• Male
• Middle Aged
• Neuraminidase (antagonists & inhibitors)
• Prodrugs
• Pyrans
• Sialic Acids
• Young Adult
• Zanamivir (administration & dosage, adverse effects, analogs & derivatives, pharmacokinetics)