RIMONABANT SR141716 IN FEMALE BABOONS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The present study will be undertaken to provide non-human primate data on the uptake, circulatory dynamics, and clearance (pharmacokinetics) of an orally-administered solution of the drug Rimonabant (SRI 417 16). Rimonabant is a recently developed anti-obesity drug that acts on a group of receptors known as the fll1docannabinoid receptors. This system of receptors is overactive in obese individuals and is related to increased food intake, altered lipid and glucose metabolism, and weight gain. Future studies are required to determine the broader metabolic effects of this agent. The present study will provide data to design the dosing protocols for future non-human primate studies that address the effects of Rimonabant on liver fat content and lipid metabolism. Three different doses of tile drug will be given to animals on three different occasions in the form of a sweet treat (banana and peanut butter). Blood samples (10) will be collected periodically for 48 hours following each administration of the agent. Concentrations of active Rimonabant will be measured in these samples and will provide the pharmacokinetic data necessary to determine the optimal dosing regimen for future studies. Presently, Rimonabant is recommended, in conjunction with diet and exercise, in obese patients and in overweight patients with type 2 diabetes or dyslipidemia. The present study and associated future investigations will provide much needed information of the effects of this agent on multiple metabolic pathways and potentially provide information on broader indications for its use.