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Multiple‐Dose Pharmacokinetics, Pharmacodynamics, and Safety of Taranabant, a Novel Selective Cannabinoid‐1 Receptor Inverse Agonist, in Healthy Male Volunteers
Author(s) -
Addy Carol,
Rothenberg Paul,
Li Susie,
Majumdar Anup,
Agrawal Nancy,
Li Hankun,
Zhong Ling,
Yuan Jinyu,
Maes Andrea,
Dunbar Stephanie,
Cote Josee,
Rosko Kim,
Dyck Kristien,
Lepeleire Inge,
Hoon Jan,
Hecken Anne,
Depré Marleen,
Knops Annemie,
Gottesdiener Keith,
Stoch Aubrey,
Wagner John
Publication year - 2008
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 - 10.1177/0091270008317591
Subject(s) - pharmacokinetics , pharmacodynamics , inverse agonist , pharmacology , dosing , medicine , agonist , cannabinoid , cannabinoid receptor , receptor
Taranabant is a cannabinoid‐1 receptor inverse agonist for the treatment of obesity. This study evaluated the safety, pharmacokinetics, and pharmacodynamics of taranabant (5, 7.5, 10, or 25 mg once daily for 14 days) in 60 healthy male subjects. Taranabant was rapidly absorbed, with a median t max of 1.0 to 2.0 hours and a t 1/2 of approximately 74 to 104 hours. Moderate accumulation was observed in C max (1.18‐ to 1.40‐fold) and AUC 0–24 h (1.5‐ to 1.8‐fold) over 14 days for the 5‐, 7.5‐, and 10‐mg doses, with an accumulation half‐life ranging from 15 to 21 hours. Steady state was reached after 13 days. After multiple‐dose administration, plasma AUC 0–24 h and C max of taranabant increased dose proportionally (5–10 mg) and increased somewhat less than dose proportionally for 25 mg. Taranabant was generally well tolerated up to doses of 10 mg and exhibited multiple‐dose pharmacokinetics consistent with once‐daily dosing.