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

¹ Merck Research Laboratories
² Hammersmith Medicines Research

^* To whom correspondence should be addressed. E-mail: carol_addy{at}merck.com.

	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- 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- 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-. 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.

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