Premium
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 Hitoshi,
Yoshiba Satoshi,
Okabe Hiromi,
Yoshihara Kazutaka
Publication year - 2010
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270009356297
Subject(s) - pharmacokinetics , neuraminidase inhibitor , pharmacology , medicine , tolerability , dosing , adverse effect , disease , covid-19 , infectious disease (medical specialty)
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.