title: The ratio of 6β-hydroxycortisol to cortisol in urine as a measure of cytochrome P450 3A activity in postmortem cases.
abstract: Poisoning can occur with chronic accumulation of a drug due to reduced metabolic capacity; conversely, under-treatment may occur due to an increased metabolic rate. Over half of all drugs are metabolized by the cytochrome P450 3A complex (CYP3A). The activity of CYP3A can be assessed by the urinary ratio of 6β-hydroxycortisol to cortisol. The aim of this study was to determine the usefulness of this ratio as a postmortem marker for determining whether altered CYP3A enzyme activity occurred prior to death. In a series of 244 postmortem cases, this ratio ranged from 0.014 to 78.6 (median 3.50). The median was significantly higher (5.14) in a subgroup of 28 cases that exhibited the presence of CYP3A-inducing drugs. In cirrhosis, the median ratio was 1.69. This pointed to a reduced metabolic capacity of CYP3A. Thus, the ratio may constitute a rough indicator of the CYP3A metabolic capacity, which could be of value in special cases.
authors.affiliation: Section of Forensic Chemistry, Department of Forensic Medicine, Faculty of Health Sciences, University of Copenhagen, Frederik V's vej 11, 3, Copenhagen, DK-2100, Denmark.
authors.forename: Lotte M
authors.initials: LM
authors.lastname: Lang
authors.forename: Kristian
authors.initials: K
authors.lastname: Linnet
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000652:urine; D002220:Carbamazepine / Q000031:analogs & derivatives / Q000652:urine; D002648:Child; D051544:Cytochrome P-450 CYP3A / Q000502:physiology*; D065701:Cytochrome P-450 CYP3A Inducers / Q000652:urine; D005260:Female; D053593:Forensic Toxicology; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives* / Q000652:urine*; D008103:Liver Cirrhosis / Q000150:complications; D008297:Male; D008875:Middle Aged; D000078330:Oxcarbazepine; D010634:Phenobarbital / Q000652:urine; D010672:Phenytoin / Q000652:urine; D055815:Young Adult
chemical_list: D015415:Biomarkers; D065701:Cytochrome P-450 CYP3A Inducers; D002220:Carbamazepine; C001380:6 beta-hydroxycortisol; D010672:Phenytoin; D051544:Cytochrome P-450 CYP3A; D000078330:Oxcarbazepine; D006854:Hydrocortisone; D010634:Phenobarbital
keywords: antiepileptics; cytochrome P450 3A; forensic science; forensic toxicology; induction; liver disease; metabolic capacity; postmortem