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Heterogeneity of CYP3A isoforms metabolizing erythromycin and cortisol
Author(s) -
Hunt Christine M,
Watkins Paul B,
Saenger Paul,
Stave Gregg M,
Barlascini Neal,
Watlington Charles O,
Wright Jackson T,
Guzelian Philip S
Publication year - 1992
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1992.3
Subject(s) - cyp3a , erythromycin , hydroxylation , demethylation , microsome , endocrinology , chemistry , medicine , cytochrome p450 , pharmacology , biology , metabolism , biochemistry , enzyme , antibiotics , gene expression , gene , dna methylation
The N ‐demethylation of erythromycin and 6β‐hydroxylation of Cortisol are both functions of the glucocorticoid‐inducible CYP3A in human liver microsomes. To determine whether 6β‐hydroxylation and erythromycin N ‐demethylation are catalyzed by similar or distinct CYP3A isoforms, erythromycin N ‐demethylase activity, as reflected by the recently described 14 [C]‐erythromycin breath test, was compared with urinary 6β‐hydroxycortisol/cortisol ratios, a measure of Cortisol 6β‐hydroxylase activity, in nine patients. Erythromycin N ‐demethylation varied fourfold and 6β‐hydroxycortisol/cortisol ratios varied sevenfold among the subjects; no correlation was found between these activities ( r 2 = 0.065). New noninvasive tests of CYP3A strongly suggest Cortisol 6β‐hydroxylation and erythromycin N ‐demethylation are performed by distinct CYP3A isoforms. Clinical Pharmacology and Therapeutics (1992) 51 , 18–23; doi: 10.1038/clpt.1992.3
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