title: Determination of psilocin and 4-hydroxyindole-3-acetic acid in plasma by HPLC-ECD and pharmacokinetic profiles of oral and intravenous psilocybin in man.
abstract: In order to investigate the pharmacokinetic properties of psilocybin (PY), the main psychoactive compound of Psilocybe mushrooms, high performance liquid chromatographic procedures with column-switching coupled with electrochemical detection (HPLC-ECD) for reliable quantitative determination of the PY metabolites psilocin (PI) and 4-hydroxyindole-3-acetic acid (4HIAA) in human plasma were established. Sample work-up includes protection of the highly unstable phenolic analytes with ascorbic acid, freeze-drying and in-vitro microdialysis. The data of two controlled clinical studies with healthy volunteers are presented. The subjects (N = 6 for both studies) received single oral PY doses of 0.224 +/- 0.02 mg/kg b.wt. (10-20 mg) and intravenous doses of 1 mg PY, respectively. Peak plasma levels of PI after oral administration of PY were measured after 105 +/- 37 min showing an average concentration of 8.2 +/- 2.8 ng PI/ml plasma. 4HIAA peak concentrations of 150 +/- 61 ng/ml plasma were found 113 +/- 41 min after ingestion of PY. After intravenous administration, a mean PI maximum plasma concentration of 12.9 +/- 5.6 ng/ml plasma was found 1.9 +/- 1.0 min after injection. The maximum plasma levels appearing within a very short period indicate a rapid dephosphorylation of PY also when administered systemically. 4HIAA was not detected after 1 mg of intravenous PY. Estimates for the absolute bioavailability of PI after oral administration of PY were 52.7 +/- 20% (N = 3).
authors.affiliation: Institute of Pharmacy, University of Bern, Switzerland.
authors.forename: F
authors.initials: F
authors.lastname: Hasler
authors.forename: D
authors.initials: D
authors.lastname: Bourquin
authors.forename: R
authors.initials: R
authors.lastname: Brenneisen
authors.forename: T
authors.initials: T
authors.lastname: Bär
authors.forename: F X
authors.initials: FX
authors.lastname: Vollenweider
mesh_terms: D000284:Administration, Oral; D000328:Adult; D002851:Chromatography, High Pressure Liquid; D004563:Electrochemistry; D005260:Female; D006213:Hallucinogens / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000097:blood*; D007275:Injections, Intravenous; D008297:Male; D011562:Psilocybin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics
chemical_list: D006213:Hallucinogens; D011562:Psilocybin; D006897:Hydroxyindoleacetic Acid; C009105:psilocin