Forensic relevance of glucuronidation in phase-II-metabolism of alcohols and drugs.
Forensic toxicology means detecting toxic or pharmacologically active substances in body fluids and organs and the evaluation and judgement of the respective results. In the legal judgement, not only the taken in active drugs, but also their metabolites are to be included. Regarding metabolism one distinguishes phase-I- and phase-II-metabolism. In the phase-I-metabolism, active substances are converted by oxidation, reduction or hydrolysis, but influencing the polarity of more lipophilic substances often not decisively. The pharmacological activity is often preserved or even increased. In phase-II-metabolism a highly hydrophilic substance--mostly glucuronic acid--is coupled to the active substances or the respective phase-I-metabolites. This reaction step decisively increases hydrophilicity of lipophilic substances, thus enhancing renal elimination and often also abolishing pharmacologically and/or toxicologically effects. Nevertheless the interaction of different drugs and alcohols in glucuronidation and the glucuronides of phase-II-metabolism still do not play a substantial role in the forensic-toxicological analysis and interpretation of results so far. However, in vitro investigations since 1999 in our lab show that such interactions are not unlikely. For valid interpretation of complex cases in the future it may become necessary not only to quantify drugs and the phase-I-metabolites but also the phase-II-metabolites and discuss possible interactions in the metabolism.
Kaeferstein
Herbert
H
Institute of Legal Medicine, University Hospital Cologne, Melatenguertel 60-62, 50823 Koeln (Cologne), Germany. herbert.kaeferstein@uk-koeln.de
D002492:Central Nervous System Depressants / Q000378:metabolism*; D004347:Drug Interactions; D000431:Ethanol / Q000378:metabolism*; D053593:Forensic Toxicology; D020719:Glucuronides / Q000378:metabolism*; D006801:Humans; D013287:Illicit Drugs / Q000378:metabolism; D050216:Metabolic Detoxication, Phase I; D050217:Metabolic Detoxication, Phase II; D008862:Microsomes, Liver / Q000201:enzymology; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010597:Pharmacogenetics
D002492:Central Nervous System Depressants; D020719:Glucuronides; D013287:Illicit Drugs; D004364:Pharmaceutical Preparations; D000431:Ethanol