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.

Using the CYP3A Activity Evaluation to Predict the Efficacy and Safety of Diazepam in Patients With Alcohol Withdrawal Syndrome

“…Since previous research demonstrated that CYP3A4 and CYP3A5 have common substrates 21,22 and that endogenous cortisol transforms to 6-beta-hydroxicortisol (6-b-HC) selectively by CYP3A isoenzyme, the metabolic ratio of 6-b-HC/ cortisol in urine can be used to evaluate the activity of CYP3A. 23 In our study, to evaluate CYP3A enzymatic activity, we determined the urinary concentration of endogenous substrate of the enzyme and its metabolite, 6-b-HC to cortisol ratio, [24][25][26][27][28] using high-performance liquid chromatographymass spectrometry (HPLC-MS/MS). [29][30][31] The results of the isoenzymes evaluation are demonstrated in arbitrary units.…”

Chemiluminescence analysis of saliva for the assessment of emotional stress in autistic children undergoing a medical examination

“…The respiratory cytochrome P450 chain is one of the components of ROS homeostasis. The activity of cytochrome P450 is assessed by the ratio of 6-beta-hydroxycortisol and cortisol in urine because this enzyme is involved in the synthesis of cortisol (Lang and Linnet, 2014; Furuta et al , 2003) (Brixius-Anderko and Scott, 2019). Here, we hypothesize that the activity of the microsomal oxidation system may correlate with the cortisol level and, consequently, reflect the level of emotional stress.…”