Multiple-dose pharmacokinetics, pharmacodynamics, and safety of taranabant, a novel selective cannabinoid-1 receptor inverse agonist, in healthy male volunteers.

Abstract

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.

• Authors: Carol Addy, Paul Rothenberg, Susie Li, Anup Majumdar, Nancy Agrawal, Hankun Li, Ling Zhong, Jinyu Yuan, Andrea Maes, Stephanie Dunbar, Josee Cote, Kim Rosko, Kristien Van Dyck, Inge De Lepeleire, Jan de Hoon, Anne Van Hecken, Marleen Depré, Annemie Knops, Keith Gottesdiener, Aubrey Stoch, John Wagner
• Journal: Journal of clinical pharmacology (J Clin Pharmacol) Vol. 48 Issue 6 Pg. 734-44 (Jun 2008) ISSN: 0091-2700 [Print] England
• PMID: 18508950 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Amides
• Anti-Obesity Agents
• Pyridines
• Receptor, Cannabinoid, CB1
• N-(3-(4-chlorophenyl)-2-(3-cyanophenyl)-1-methylpropyl)-2-methyl-2-((5-(trifluoromethyl)pyridin-2-yl)oxy)propanamide

Topics

• Adult
• Amides (administration & dosage, adverse effects, pharmacokinetics)
• Anti-Obesity Agents (administration & dosage, adverse effects, pharmacokinetics)
• Area Under Curve
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug Administration Schedule
• Drug Inverse Agonism
• Half-Life
• Humans
• Male
• Middle Aged
• Obesity (drug therapy)
• Pyridines (administration & dosage, adverse effects, pharmacokinetics)
• Receptor, Cannabinoid, CB1 (drug effects)