The Ratio of 6β-Hydroxycortisol to Cortisol in Urine as a Measure of Cytochrome P450 3A Activity in Postmortem Cases

TY - JOUR

T1 - The Ratio of 6β-Hydroxycortisol to Cortisol in Urine as a Measure of Cytochrome P450 3A Activity in Postmortem Cases

AU - Lang, Lotte Markussen

AU - Linnet, Kristian

PY - 2014/7

Y1 - 2014/7

N2 - 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.

AB - 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.

U2 - 10.1111/1556-4029.12418

DO - 10.1111/1556-4029.12418

M3 - Journal article

C2 - 24611975

SN - 0022-1198

VL - 59

SP - 1036

EP - 1040

JO - Journal of Forensic Sciences

JF - Journal of Forensic Sciences

IS - 4

ER -