Concentration-time profiles of gamma-hydroxybutyrate in blood after recreational doses are best described by zero-order rather than first-order kinetics.
The recreational drug gamma-hydroxybutyrate (GHB) has a short plasma elimination half-life (t(1/2)) reported to be about 30-50 min. However, this represents a terminal half-life and therefore might not necessarily apply after large (abuse) doses are taken. Clinical studies with sodium oxybate (sodium salt of GHB) suggest that zero-order rather than first-order kinetics are more appropriate to describe post-peak concentration-time (C-T) profiles. We report the case of a 23-year-old male found unconscious by the police and a blood sample contained 100 mg/L GHB and 0.14 g% ethanol. On regaining consciousness the man admitted drinking alcohol about 6 h earlier but claimed that his drink must have been spiked with GHB. The police wanted to know how much GHB had been administered to account for the man's clinical condition. A back-calculation for 6 h, assuming a GHB half-life of 40 min, gives a very high concentration in blood of approximately 900 mg/L, which would probably have proven fatal. Back-calculating using zero-order kinetics and a proposed elimination rate of 18 mg/L per hour leads to a GHB concentration of 208 mg/L, which is much more realistic. Toxicologists should not arbitrarily apply the principles of first-order kinetics after abuse doses of drugs, when zero-order or saturation kinetics (Michaelis-Menten) are more appropriate.
Jones
A W
AW
Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Artillerigatan 12, 587 58 Linköping, Sweden. wayne.jones@RMV.se
Eklund
A
A
Kronstrand
R
R
D000328:Adult; D018686:Anesthetics, Intravenous / Q000097:blood* / Q000493:pharmacokinetics / Q000506:poisoning; D002849:Chromatography, Gas; D000431:Ethanol / Q000097:blood; D005410:Flame Ionization; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D008297:Male; D015233:Models, Statistical; D012978:Sodium Oxybate / Q000097:blood* / Q000493:pharmacokinetics / Q000506:poisoning; D019966:Substance-Related Disorders / Q000097:blood*; D055815:Young Adult
D018686:Anesthetics, Intravenous; D000431:Ethanol; D012978:Sodium Oxybate