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PMID: 2590599 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

British journal of clinical pharmacology ·Vol. 28 ·No. 4 ·1989-10-00 ·Pages 373-87

Ged C, Rouillon JM, Pichard L, Combalbert J, Bressot N, Bories P, Michel H, Beaune P, Maurel P

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.

MeSH Terms
Adult Aged Biomarkers Chromatography, High Pressure Liquid Cytochrome P-450 Enzyme System/biosynthesis Enzyme Induction/drug effects Female Humans Hydrocortisone/analogs & derivatives,urine Immunoblotting Isoenzymes/biosynthesis Liver/enzymology Male Microsomes, Liver/enzymology Middle Aged Mixed Function Oxygenases/metabolism Rifampin/pharmacology Tissue Donors
Chemicals
Biomarkers Isoenzymes 6 beta-hydroxycortisol Cytochrome P-450 Enzyme System Mixed Function Oxygenases Rifampin Hydrocortisone
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Ged C
INSERM U 75, Hôpital Necker-Enfants Malades, Paris, France.
Rouillon J M
Pichard L
Combalbert J
Bressot N
Bories P
Michel H
Beaune P
Maurel P
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Article Info
Journal
British journal of clinical pharmacology
Abbr.
Br J Clin Pharmacol
ISSN
0306-5251
DOI
10.1111/j.1365-2125.1989.tb03516.x
Published
1989-10-00
Pages
373-87
Language
English
Region
England
NLM ID
7503323
PMCID
PMC1379986
Subset
IM
External Links
PubMed source DOI: 10.1111/j.1365-2125.1989.tb03516.x PMC Full Text View journal details
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