Safety, tolerability, pharmacokinetics, and pharmacodynamic properties of taranabant, a novel selective cannabinoid-1 receptor inverse agonist, for the treatment of obesity: results from a double-blind, placebo-controlled, single oral dose study in healthy volunteers.

Abstract

Taranabant is a novel cannabinoid CB-1 receptor (CB1R) inverse agonist in clinical development for the treatment of obesity. This double-blind, randomized, placebo-controlled, single oral dose study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of taranabant (0.5-600 mg) in 24 healthy male volunteers. Single-dose AUC(0-infinity) and C(max) values for taranabant increased approximately linearly with dose up to 200 mg, with slightly less than dose-proportional increases in AUC(0-infinity) and C(max) values for doses >200 mg. Plasma taranabant had a biphasic disposition, with a median t(max) of 1 to 2.5 hours and a terminal elimination t((1/2)) of 38 to 69 hours. Coadministration of taranabant with a high-fat meal led to a 14% increase in C(max) and a 74% increase in AUC(0-infinity). Clinical adverse experiences associated with single doses of taranabant were generally mild and transient. Of the 198 clinical adverse experiences reported, the most common drug-related ones were nausea (36), headache (22), drowsiness (14), abdominal discomfort/abdominal pain/stomachache (14), hiccups (9), dizziness (8), decreased appetite (7), increased bowel movement (7), mood change (6), tiredness (4), vomiting (4), and sweating increased (4). Taranabant has pharmacokinetic characteristics suitable for a once-daily dosing regimen.

• Authors: Carol Addy, Susie Li, Nancy Agrawal, Julie Stone, Anup Majumdar, Ling Zhong, Hankun Li, Jinyu Yuan, Andrea Maes, Paul Rothenberg, Josee Cote, Kim Rosko, Corinne Cummings, Steven Warrington, Malcolm Boyce, Keith Gottesdiener, Aubrey Stoch, John Wagner
• Journal: Journal of clinical pharmacology (J Clin Pharmacol) Vol. 48 Issue 4 Pg. 418-27 (Apr 2008) ISSN: 0091-2700 [Print] England
• PMID: 18258750 (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

• Adolescent
• Adult
• Amides (adverse effects, pharmacokinetics, pharmacology)
• Analysis of Variance
• Anti-Obesity Agents (adverse effects, pharmacokinetics, pharmacology)
• Area Under Curve
• Dose-Response Relationship, Drug
• Double-Blind Method
• Female
• Half-Life
• Humans
• Male
• Pyridines (adverse effects, pharmacokinetics, pharmacology)
• Receptor, Cannabinoid, CB1 (agonists)