Disposition of gamma-hydroxybutyric acid in conventional and nonconventional biologic fluids after single drug administration: issues in methodology and drug monitoring

Ther Drug Monit. 2007 Feb;29(1):64-70. doi: 10.1097/FTD.0b013e3180307e5e.

Abstract

Little controlled drug administration data are available to aid in the interpretation of gamma-hydroxybutyric acid (GHB) distribution in conventional and nonconventional fluids and the potential correlation between the pharmacokinetics of GHB and drug effects. Single oral sodium GHB doses of 50 mg/kg were administered to five volunteers. Plasma, oral fluid, urine, and sweat were analyzed for GHB by gas chromatography-mass spectrometry. GHB stability in plasma was studied at different storage temperatures. Subjective effects were measured using a set of 13 different visual analog scales. Mean peak GHB plasma concentrations at 30 minutes were 83.1 microg/mL. After the absorption phase, concentrations declined to mean values of 0.9 microg/mL at 6 hours. GHB was found in oral fluid at peak value concentrations equivalent to one third to one fourth of those found in plasma. The oral fluid-to-plasma ratio varied two fold in the 1- to 6-hour time range but always was lower than unit. The mean half-life (t1/2) of GHB was approximately 0.7 hour in plasma and approximately 1.2 hours in oral fluid. GHB urinary excretion is less than 2% of the dose administered. GHB was also detected in sweat at low concentrations. GHB showed a mixed sedative-stimulant pattern with subjective effects peaking between 1 and 1.5 hours after drug administration and lasting for 2 hours. Oral fluid and sweat appeared not to be suitable biologic matrices for monitoring GHB consumption. GHB-mediated subjective effects are related to GHB plasma concentrations.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Area Under Curve
  • Drug Monitoring / methods*
  • Drug Stability
  • Half-Life
  • Humans
  • Hydroxybutyrates / blood
  • Hydroxybutyrates / pharmacokinetics*
  • Hydroxybutyrates / urine
  • Male
  • Reproducibility of Results
  • Saliva / metabolism
  • Sweat / metabolism
  • Temperature
  • Time Factors
  • Tissue Distribution

Substances

  • Hydroxybutyrates
  • 4-hydroxybutyric acid