COMPARISON OF URINARY 6-BETA-CORTISOL AND THE ERYTHROMYCIN BREATH TEST AS MEASURES OF HEPATIC P450IIIA (CYP3A) ACTIVITY

被引:121
作者
WATKINS, PB
TURGEON, DK
SAENGER, P
LOWN, KS
KOLARS, JC
HAMILTON, T
FISHMAN, K
GUZELIAN, PS
VOORHEES, JJ
机构
[1] UNIV MICHIGAN, MED CTR, DEPT DERMATOL, ANN ARBOR, MI 48109 USA
[2] YESHIVA UNIV ALBERT EINSTEIN COLL MED, MONTEFIORE MED CTR, DEPT PEDIAT, BRONX, NY 10461 USA
[3] VIRGINIA COMMONWEALTH UNIV, MED COLL VIRGINIA, DEPT MED, RICHMOND, VA 23298 USA
关键词
D O I
10.1038/clpt.1992.140
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The prodUction of (CO2)-C-14 in the breath from an intravenous dose of [C-14-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 < 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 fiver 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.
引用
收藏
页码:265 / 273
页数:9
相关论文
共 31 条
[1]  
ANNESLEY T, 1986, CLIN CHEM, V32, P1407
[2]   CLINICAL UTILITY OF BREATH TESTS FOR THE ASSESSMENT OF HEPATIC-FUNCTION [J].
BAKER, AL ;
KOTAKE, AN ;
SCHOELLER, DA .
SEMINARS IN LIVER DISEASE, 1983, 3 (04) :318-329
[3]   LIDOCAINE METABOLISM IN HUMAN-LIVER MICROSOMES BY CYTOCHROME-P450IIIA4 [J].
BARGETZI, MJ ;
AOYAMA, T ;
GONZALEZ, FJ ;
MEYER, UA .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 1989, 46 (05) :521-527
[4]  
BIENVENU T, 1991, INT J CLIN PHARM TH, V29, P441
[5]   THE INCREASE IN URINARY-EXCRETION OF 6-BETA-HYDROXYCORTISOL AS A MARKER OF HUMAN HEPATIC CYTOCHROME-P450IIIA INDUCTION [J].
GED, C ;
ROUILLON, JM ;
PICHARD, L ;
COMBALBERT, J ;
BRESSOT, N ;
BORIES, P ;
MICHEL, H ;
BEAUNE, P ;
MAUREL, P .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 1989, 28 (04) :373-387
[6]  
GUENGERICH FP, 1986, J BIOL CHEM, V261, P5051
[7]  
GUENGERICH FP, 1989, ANNU REV PHARMACOL, V29, P241
[8]   HETEROGENEITY OF CYP3A ISOFORMS METABOLIZING ERYTHROMYCIN AND CORTISOL [J].
HUNT, CM ;
WATKINS, PB ;
SAENGER, P ;
STAVE, GM ;
BARLASCINI, N ;
WATLINGTON, CO ;
WRIGHT, JT ;
GUZELIAN, PS .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 1992, 51 (01) :18-23
[9]   IDENTIFICATION OF THE CYTOCHROME-P450 IIIA FAMILY AS THE ENZYMES INVOLVED IN THE N-DEMETHYLATION OF TAMOXIFEN IN HUMAN LIVER-MICROSOMES [J].
JACOLOT, F ;
SIMON, I ;
DREANO, Y ;
BEAUNE, P ;
RICHE, C ;
BERTHOU, F .
BIOCHEMICAL PHARMACOLOGY, 1991, 41 (12) :1911-1919
[10]   RADIOIMMUNOASSAY OF 6-BETA-HYDROXYCORTISOL IN HUMAN-PLASMA AND URINE [J].
KISHIDA, S ;
FUKUSHIMA, DK .
STEROIDS, 1977, 30 (06) :741-749