title: Pharmacokinetics of the plant-derived kappa-opioid hallucinogen salvinorin A in nonhuman primates.
abstract: Salvinorin A, a potent hallucinogen isolated from the leaves of Salvia divinorum, has gained popularity among adolescents in the USA. No detailed study of the pharmacokinetics has been conducted in vivo. The present study investigates the in vivo pharmacokinetics of salvinorin A (0.032 mg/kg, i.v. bolus) in rhesus monkeys (n=4, 2 male, 2 female). The elimination t(1/2) was rapid (56.6+/-24.8 min) for all subjects. Pharmacokinetic differences (distribution t(1/2), elimination t(1/2), and AUC) were observed between males and females, suggesting potential sex differences in its pharmacologic effects. Salvinorin B, the presumed major metabolite, is observed to accumulate ex vivo; however, in this study it never reached the limit of detection.
authors.affiliation: Division of Medicinal & Natural Products Chemistry, The University of Iowa, Iowa City, Iowa 52242.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Schmidt
authors.forename: Mark S
authors.initials: MS
authors.lastname: Schmidt
authors.forename: Eduardo R
authors.initials: ER
authors.lastname: Butelman
authors.forename: Wayne W
authors.initials: WW
authors.lastname: Harding
authors.forename: Kevin
authors.initials: K
authors.lastname: Tidgewell
authors.forename: Daryl J
authors.initials: DJ
authors.lastname: Murry
authors.forename: Mary Jeanne
authors.initials: MJ
authors.lastname: Kreek
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Prisinzano
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004224:Diterpenes / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D045785:Diterpenes, Clerodane; D005260:Female; D006213:Hallucinogens / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D007275:Injections, Intravenous; D008253:Macaca mulatta; D008297:Male; D008657:Metabolic Clearance Rate / Q000502:physiology; D009294:Narcotics / Q000097:blood / Q000493:pharmacokinetics; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000378:metabolism; D012727:Sex Characteristics; D013997:Time Factors
chemical_list: D004224:Diterpenes; D045785:Diterpenes, Clerodane; D006213:Hallucinogens; D006993:Hypnotics and Sedatives; D009294:Narcotics; D017473:Receptors, Opioid, kappa; C090499:salvinorin A