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Study of the absorption, metabolism, and excretion of ( 14 C)‐ramelteon (TAK‐375)
Author(s) -
Stevenson S.,
Cornelissen K.,
Clarke E.,
Hibberd M.
Publication year - 2004
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2003.11.084
Subject(s) - metabolite , chemistry , pharmacokinetics , pharmacology , metabolism , excretion , active metabolite , clinical pharmacology , medicine , biochemistry
This study investigated the pharmacokinetics, metabolism and excretion of ramelteon, a novel selective ML 1 receptor agonist. Six healthy male subjects received a single oral dose of 16 mg ( 14 C)‐ramelteon. Ramelteon was rapidly absorbed (t max of 0.3 hours) and eliminated (half‐life of 1.2 hours). The metabolites MI, MI, MI11 and MIV were rapidly formed and eliminated (half‐lives of 1 to 3 hours). Systemic exposure of metabolite M‐II (major active metabolite) was 20‐ to 30‐fold greater than that of ramelteon, while the exposures of M‐I, M‐III, and M‐IV were one‐ to four‐fold higher than that of ramelteon. Of total radioactivity administered, 84% was renally eliminated, and 4% was faecally eliminated, with metabolites of ramelteon accounting for the majority of the dose eliminated. High urinary recovery of radioactivity indicates that there was at least 84% oral absorption of ramelteon. Negligible urinary excretion of ramelteon and low serum concentrations of ramelteon (relative to metabolites) indicate that ramelteon undergoes extensive first‐pass metabolism. Ramelteon was metabolized primarily via oxidation to hydroxyl and carbonyl groups, with secondary metabolism to form glucuronide conjugates. Clinical Pharmacology & Therapeutics (2004) 75 , P22–P22; doi: 10.1016/j.clpt.2003.11.084