Disposition of gamma-hydroxybutyric acid in conventional and nonconventional biologic fluids after single drug administration: issues in methodology and drug monitoring.
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.
Abanades
Sergio
S
Pharmacology Research Unit, Human Pharmacology and Clinical Neurosciences Research Group, Institut Municipal d'Investigació Mèdica, Barcelona, Spain.
Farré
Magi
M
Segura
Mireia
M
Pichini
Simona
S
Pastor
Antoni
A
Pacifici
Roberta
R
Pellegrini
Manuela
M
de la Torre
Rafael
R
D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D016903:Drug Monitoring / Q000379:methods*; D004355:Drug Stability; D006207:Half-Life; D006801:Humans; D006885:Hydroxybutyrates / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D008297:Male; D015203:Reproducibility of Results; D012463:Saliva / Q000378:metabolism; D013542:Sweat / Q000378:metabolism; D013696:Temperature; D013997:Time Factors; D014018:Tissue Distribution
D006885:Hydroxybutyrates; C111420:4-hydroxybutyric acid