The increase in urinary excretion of 6 beta-hydroxycortisol as a marker of human hepatic cytochrome P450IIIA induction.

doi:10.1111/J.1365-2125.1989.TB03516.X

Paper

The increase in urinary excretion of 6 beta-hydroxycortisol as a marker of human hepatic cytochrome P450IIIA induction.

Published Oct 1, 1989 · C. Ged, J. Rouillon, L. Pichard

British journal of clinical pharmacology

Q1 SJR score

354

Citations

8

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Abstract

1. Urinary excretion of 6 beta-hydroxycortisol, hepatic microsomal cortisol 6 beta-hydroxylase and the specific content of several forms of cytochrome P450 were measured in 8 to 14 patients before and after treatment with rifampicin (600 mg orally per day for 4 days). 2. Rifampicin treatment produced an average five fold increase in daily excretion of urinary 6 beta-hydroxycortisol. 3. Cortisol 6 beta-hydroxylase activity increased from 15 +/- 6 pmol min-1 mg-1 in organ donors (considered as 'control subjects') to 87 +/- 31 pmol min-1 mg-1 in rifampicin treated patients. 4. Among three forms of human P450 (P450IA, IIC and IIIA), (1), (2), measured by Western blots, only P450IIIA was significantly induced by the antibiotic. 5. Only antibodies against P450IIIA selectively inhibited cortisol 6 beta-hydroxylase in human liver microsomes. 6. Cortisol 6 beta-hydroxylase was correlated with P450IIIA specific content. 7. The urinary level of 6 beta-hydroxycortisol correlated with liver microsomal cortisol 6 beta-hydroxylase and P450IIIA specific content. 8. We conclude that P450IIIA is predominantly responsible for cortisol 6 beta-hydroxylase activity in human liver microsomes and that urinary 6 beta-hydroxycortisol is a marker of the induction of this cytochrome P450.

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Study Snapshot

Urinary 6 beta-hydroxycortisol levels increase during rifampicin treatment, indicating that P450IIIA is primarily responsible for cortisol 6 beta-hydroxylase activity in human liver microsomes.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

The increase in urinary excretion of 6 beta-hydroxycortisol as a marker of human hepatic cytochrome P450IIIA induction.

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References

Metabolism of cyclosporin A. IV. Purification and identification of the rifampicin-inducible human liver cytochrome P-450 (cyclosporin A oxidase) as a product of P450IIIA gene subfamily.

P-450(CsA) is responsible for 80% of cyclosporin A oxidase activity in human liver, is encoded by gene P450IIIA3, and is strongly inducible by rifampicin pretreatment.

Characterization of cDNAs, mRNAs, and proteins related to human liver microsomal cytochrome P-450 (S)-mephenytoin 4'-hydroxylase.

The MP-4/MP-8 gene products are likely involved in mephenytoin 4'-hydroxylation, and variations in catalytic activity among individuals may be due to base differences in the structural gene(s).

A novel human cytochrome P450 gene (P450IIB): chromosomal localization and evidence for alternative splicing

The human P450IIB gene, a less extensive subfamily than rodent homologues, has been identified and mapped to chromosome 19q12--19q13.2, with potential linkage to CYP 2A locus.

Human liver microsomal steroid metabolism: identification of the major microsomal steroid hormone 6 beta-hydroxylase cytochrome P-450 enzyme.

P-450 NF or a closely related enzyme is the major catalyst of steroid hormone 6 hydroxylation in human liver microsomes, suggesting it could serve as a noninvasive monitor for this enzyme's activity.

Involvement of the macrolide antibiotic inducible cytochrome P-450 LM3c in the metabolism of midazolam by microsomal fractions prepared from rabbit liver.

The rabbit cytochrome P-450 LM3c isozyme is predominantly involved in midazolam metabolism, with LM3c being induced by macrolide antibiotics.

Citations

Postprandial hypoglycemia caused by the combination of clarithromycin and rifampicin in a patient with nontuberculous mycobacterial pulmonary disease.

The combination of clarithromycin and rifampicin can cause postprandial hypoglycemia in patients with nontuberculous mycobacterial pulmonary disease, and shifting administration from morning to before sleep can correct the issue.

Novel Approaches to Characterize Individual Drug Metabolism and Advance Precision Medicine

Novel approaches, such as evaluating circulating noncoding RNAs and liquid biopsy-derived markers, can advance precision medicine by identifying individual drug metabolism phenotypes and individualized drug treatment strategies.

Reevaluate In Vitro CYP3A Index Reactions of Benzodiazepines and Steroids between Humans and Dogs

Canine CYP2B11 contributes significantly to benzodiazepine hydroxylation, while CYP3A12 and CYP3A26 primarily catalyze CYP3A index reactions in humans and dogs, respectively.

Predicting drug–drug interactions by electrochemically driven cytochrome P450 3A4 reactions

Electrochemically driven cytochrome P450 3A4 models can effectively predict drug-drug interactions, with a more positive potential of onset of catalysis indicating a more pronounced role of drug as leading medication.

Studies on CYP3A activity during the menstrual cycle as measured by urinary 6β‐hydroxycortisol/cortisol

Gut microbiota may affect CYP3A activity during the menstrual cycle, with a significant association found between urinary 6OHC/C and TMAO levels in serum.