CLINICAL PHARMACOKINETICS OF ESCALATING IV DOSES OF DEXANABINOL (HU-211), A NEUROPROTECTANT AGENT, IN NORMAL VOLUNTEERS

The pharmacokinetics of dexanabinol (HU-211), a synthetic, nonpsychotr opic cannabinoid with neuroprotectant action, was evaluated in a phase I clinical trial. The compound was administered at doses of 48 mg, 10 0 mg, and 200 mg as short i.v. infusions in a Cremophor-ethanol vehicl e diluted with saline. All administrations were well-tolerated and no compound-related side-effects were observed. Plasma concentrations of dexanabinol were quantitated using a GC/MS/MS technique which provided a limit of quantitation of 100 pg/ml. The elimination of dexanabinol was best fitted to a 3-compartment model with a rapid distribution hal f-life (< 5 min), an intermediate phase half-life of approximately 90 min, and a slow terminal elimination half-life (similar to 9 h). The p harmacokinetics were linear over the evaluated dose range. The plasma clearance of the drug was high (1,700 ml/min) and the volume of distri bution approximately 151/kg. These data are similar to those reported for naturally occurring cannabinoids such as Delta(9)-tetrahydrocannab inol and cannabidiol.