Heterogeneity of CYP3A isoforms metabolizing erythromycin and cortisol.
The N-demethylation of erythromycin and 6 beta-hydroxylation of cortisol are both functions of the glucocorticoid-inducible CYP3A in human liver microsomes. To determine whether 6 beta-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 6 beta-hydroxycortisol/cortisol ratios, a measure of cortisol 6 beta-hydroxylase activity, in nine patients. Erythromycin N-demethylation varied fourfold and 6 beta-hydroxycortisol/cortisol ratios varied sevenfold among the subjects; no correlation was found between these activities (r2 = 0.065). New noninvasive tests of CYP3A strongly suggest cortisol 6 beta-hydroxylation and erythromycin N-demethylation are performed by distinct CYP3A isoforms.
Hunt
C M
CM
Department of Medicine, Medical College of Virginia, Richmond.
Watkins
P B
PB
Saenger
P
P
Stave
G M
GM
Barlascini
N
N
Watlington
C O
CO
Wright
J T
JT
Guzelian
P S
PS
D000368:Aged; D001944:Breath Tests; D002250:Carbon Radioisotopes; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D004110:Diltiazem / Q000494:pharmacology; D004917:Erythromycin / Q000378:metabolism*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism* / Q000652:urine; D006900:Hydroxylation; D006973:Hypertension / Q000097:blood / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D008297:Male; D008745:Methylation; D008875:Middle Aged; D012727:Sex Characteristics
D002250:Carbon Radioisotopes; D007527:Isoenzymes; C001380:6 beta-hydroxycortisol; D004917:Erythromycin; D003577:Cytochrome P-450 Enzyme System; D004110:Diltiazem; D006854:Hydrocortisone