title: Clinical pharmacokinetics of escalating i.v. doses of dexanabinol (HU-211), a neuroprotectant agent, in normal volunteers.
abstract: The pharmacokinetics of dexanabinol (HU-211), a synthetic, nonpsychotropic cannabinoid with neuroprotectant action, was evaluated in a phase I clinical trial. The compound was administered at doses of 48 mg, 100 mg, and 200 mg as short i.v. infusions in a Cremophor-ethanol vehicle 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 half-life (< 5 min), an intermediate phase half-life of approximately 90 min, and a slow terminal elimination half-life (approximately 9 h). The pharmacokinetics were linear over the evaluated dose range. The plasma clearance of the drug was high (1,700 ml/min) and the volume of distribution approximately 15 l/kg. These data are similar to those reported for naturally occurring cannabinoids such as delta 9-tetrahydrocannabinol and cannabidiol.
authors.affiliation: Pharmos Corporation, Alachua, FL, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Brewster
authors.forename: E
authors.initials: E
authors.lastname: Pop
authors.forename: R L
authors.initials: RL
authors.lastname: Foltz
authors.forename: S
authors.initials: S
authors.lastname: Reuschel
authors.forename: W
authors.initials: W
authors.lastname: Griffith
authors.forename: S
authors.initials: S
authors.lastname: Amselem
authors.forename: A
authors.initials: A
authors.lastname: Biegon
mesh_terms: D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D013759:Dronabinol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D018696:Neuroprotective Agents; D013759:Dronabinol; C062018:HU 211