Concentration-time profiles of gamma-hydroxybutyrate in blood after recreational doses are best described by zero-order rather than first-order kinetics

J Anal Toxicol. 2009 Jul-Aug;33(6):332-5. doi: 10.1093/jat/33.6.332.

Abstract

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.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Anesthetics, Intravenous / blood*
  • Anesthetics, Intravenous / pharmacokinetics
  • Anesthetics, Intravenous / poisoning
  • Chromatography, Gas
  • Ethanol / blood
  • Flame Ionization
  • Half-Life
  • Humans
  • Kinetics
  • Male
  • Models, Statistical
  • Sodium Oxybate / blood*
  • Sodium Oxybate / pharmacokinetics
  • Sodium Oxybate / poisoning
  • Substance-Related Disorders / blood*
  • Young Adult

Substances

  • Anesthetics, Intravenous
  • Ethanol
  • Sodium Oxybate