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

被引：37

作者：

Addy, Carol ^{[1
]}

Li, Susie ^{[2
]}

Agrawal, Nancy ^{[2
]}

Stone, Julie ^{[2
]}

Majumdar, Anup ^{[2
]}

Zhong, Ling ^{[2
]}

Li, Hankun ^{[2
]}

Yuan, Jinyu ^{[3
]}

Maes, Andrea ^{[3
]}

Rothenberg, Paul ^{[3
]}

Cote, Josee ^{[3
]}

Rosko, Kim ^{[3
]}

Cummings, Corinne ^{[4
]}

Warrington, Steven ^{[5
]}

Boyce, Malcolm ^{[5
]}

Gottesdiener, Keith ^{[3
]}

Stoch, Aubrey ^{[3
]}

Wagner, John ^{[3
]}

机构：

[1] Merck Res Labs, Boston, MA 02115 USA

[2] Merck Res Labs, West Point, PA USA

[3] Merck Res Labs, Rahway, NJ USA

[4] Merck Res Labs, Harlow, Essex, England

[5] Cent Middlesex Hosp, London NW10 7NS, England

来源：

JOURNAL OF CLINICAL PHARMACOLOGY | 2008年 / 48卷 / 04期

关键词：

MK-0364; taranabant; cannabinoid-1 receptor inverse agonist; obesity; appetite; satiety;

D O I：

10.1177/0091270008314467

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Taranabant is a novel cannabinoid CB-1 receptor (CBM) 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 toranabont (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.

引用

页码：418 / 427

页数：10

共 31 条

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