No abstract

In Europe, the misuse of gamma-hydroxybutyric acid (GHB) and its analogues has increased within the recent years. Here, 2 fatalities and 1 nonfatal intoxication resulting from ingestion of gamma-butyrolactone (GBL), a precursor of GHB, are presented. GHB was quantified involving the conversion to GBL by application of a gas chromatography-mass spectrometry (GC/MS) method. Besides quantitation of GHB equivalents ("total GBL"), all specimens of case 1 were analyzed for the metabolic precursor GBL itself (absolute GBL). The cause of death in each case was attributed to GHB intoxication; the manner of death was suicide in the first case and accidental in the second one. Another yet nonfatal GHB intoxication was reported by an emergency department concerning a 36-year-old woman who was hospitalized due to her comatose state and loss of adverse effects reflexes. Here nail polish remover pads were used as source for GBL.

No abstract

The conversion of 1,4-butanediol (1,4-BD) to gamma-hydroxybutyric acid (GHB), a drug of abuse, is most probably catalyzed by alcohol dehydrogenase, and potentially by aldehyde dehydrogenase. The purpose of this study was to investigate the degradation of 1,4-BD in cytosolic supernatant of human liver in vitro, and to verify involvement of the suggested enzymes by means of gas chromatography-mass spectrometry. The coingestion of 1,4-BD and ethanol (EtOH) might cause complex pharmacokinetic interactions in humans. Therefore, the effect of EtOH on 1,4-BD metabolism by human liver was examined in vitro. Additionally, the influence of acetaldehyde (AL), which might inhibit the second step of 1,4-BD degradation, was investigated. In case of a 1,4-BD intoxication, the alcohol dehydrogenase inhibitor fomepizole (4-methylpyrazole, FOM) has been discussed as an antidote preventing the formation of the central nervous system depressing GHB. Besides FOM, we tested pyrazole, disulfiram, and cimetidine as possible inhibitors of the formation of GHB from 1,4-BD catalyzed by human liver enzymes in vitro. The conversion of 1,4-BD to GHB was inhibited competitively by EtOH with an apparent K(i) of 0.56 mM. Therefore, the coingestion of 1,4-BD and EtOH might increase the concentrations and the effects of 1,4-BD itself. By contrast AL accelerated the formation of GHB. All antidotes showed the ability to inhibit the formation of GHB. In comparison FOM showed the highest inhibitory effectiveness. Furthermore, the results confirm strong involvement of ADH in 1,4-BD metabolism by human liver.