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Tuesday, August 26 Metabolism and Disposition of Drugs

Helander A., Jones A.W.*, Bendtsen P.*
Dept. of Clinical Neuroscience, St. Gorans Hospital, Karolinska Institute, Stockholm and * Dept. of Forensic Toxicology and Drug Dependence Unit, University Hospital, Linkoping, Sweden

The traditional way to establish whether a person has been drinking is by the analysis of breath, blood or urine samples for the presence of ethanol. However, because ethanol is rapidly metabolised and eliminated from the body, a method to reveal recent drinking even after ethanol has been cleared would have considerable importance in clinical and forensic toxicology. This study compared the analysis of urinary methanol with that of 5-hydroxytryptophol (5HTOL), a metabolite of serotonin, as biochemical markers of recent drinking.

Methods. Healthy volunteers drank 50 or 80 g alcohol within 2 h in the evening together with a meal. Urine was voided before drinking started, twice during the evening, and on 3 occasions the next morning or early afternoon. Other volunteers received an intravenous infusion of ethanol (0.4 g/kg over 30 min) on two separate days. Urine was voided before ethanol infusion and at 1-h intervals after the start for a total of 8 h. The breath-alcohol content was measured with an infrared analyser, and urinary concentrations of ethanol and methanol were determined by headspace GC. The serotonin metabolites 5HTOL and 5HIAA were analysed by GC/MS and HPLC, respectively.

Results. The concentrations of methanol and 5HTOL (expressed as a ratio to 5HIAA) were displaced in time by several hours compared with breath and urinary ethanol, and remained elevated in the first, second and sometimes the third urinary voids collected the next morning or early afternoon. The concentration-time profiles of the markers after infusion of ethanol showed large variations between subjects but good agreement existed within the same subject from day to day.

Conclusions. The time-lag of methanol and the 5HTOL/5HIAA ratio compared with ethanol forms an objective basis of testing for recent drinking even after the alcohol has left the body. Potential applications might include documentation of drinking during rehabilitation of alcoholics (relapse) and drunk drivers, and in workplace testing such as after a serious accident (hangover effect).

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