Comparison of urinary 6-beta-cortisol and the erythromycin breath test as measures of hepatic P450IIIA (CYP3A) activity.
The production of 14CO2 in the breath from an intravenous dose of [14C-N-methyl]-erythromycin (the erythromycin breath test [ERMBT]) and the measurement of the ratio of 6-beta-cortisol to free cortisol (6-beta-F/FF) in the urine have each been proposed as means of measuring hepatic P450IIIA catalytic activity in patients. We found that there was a significant correlation between the results of each test (r = 0.59, p less than 0.001) in 47 patients who were without liver disease and who were not taking medications believed to influence P450IIIA catalytic activity. In the 24 of these patients who were subsequently treated with the P450IIIA substrate cyclosporine, the ERMBT result was highly correlated with the mean trough cyclosporine blood level observed; however, there was no correlation between urinary 6-beta-F/FF and the cyclosporine blood levels. In a separate study of a patient during the anhepatic phase of liver transplantation surgery, the ERMBT result decreased by greater than 85%, whereas urinary 6-beta-F/FF decreased by just 50%. We conclude that the ERMBT and urinary 6-beta-F/FF do not always provide similar information about P450IIIA catalytic activity in patients, possibly because of extrahepatic production of 6-beta-F. Of the two tests, the ERMBT appears to provide the most relevant information for cyclosporine administration.
Watkins
P B
PB
Department of Medicine, University of Michigan Medical Center, Ann Arbor, MI 48109-0108.
Turgeon
D K
DK
Saenger
P
P
Lown
K S
KS
Kolars
J C
JC
Hamilton
T
T
Fishman
K
K
Guzelian
P S
PS
Voorhees
J J
JJ
D001189:Aryl Hydrocarbon Hydroxylases; D001944:Breath Tests / Q000379:methods*; D002245:Carbon Dioxide / Q000378:metabolism; D016572:Cyclosporine / Q000627:therapeutic use; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000652:urine*; D008099:Liver / Q000201:enzymology*; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism*; D011565:Psoriasis / Q000188:drug therapy; D012044:Regression Analysis; D012293:Rifampin / Q000627:therapeutic use; D014217:Troleandomycin / Q000627:therapeutic use
D002245:Carbon Dioxide; D016572:Cyclosporine; D003577:Cytochrome P-450 Enzyme System; D014217:Troleandomycin; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating; D012293:Rifampin; D006854:Hydrocortisone