Caffeine test in predicting flutamide-induced hepatic injury in patients with prostate cancer.
The caffeine test measures the activity of cytochrome p450 (CYP1A2) which is a major enzyme involved in the activation of flutamide. The usefulness of this test in predicting flutamide-induced hepatic injury in patients with prostate cancer was examined. The subjects were: (1). five patients whose aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level rose to 100 IU/l or higher following the start of flutamide (moderately injured group); (2). four patients whose AST and ALT levels were higher than normal but less than 100 IU/l (mildly injured group); and (3). two patients whose hepatic function remained normal (normal group). The subjects were each given canned coffee to drink. Urinary caffeine (137X), paraxanthine (17X) and 1, 7-dimethyluric acid (17U) levels were measured 4-5 h later. The metabolite ratio, (17U+17X)/137X, was calculated to serve as an indicator of CYP1A2 activity. The metabolite ratio for the moderately injured group (3.98+/-1.56) and the mildly injured group (5.55+/-1.42) were lower than that for the normal group (9.56). The results suggest that a decrease in CYP1A2 activity is involved in the onset of flutamide-induced hepatic injury, and that the caffeine test seems to provide a useful means of its prediction.
Ozono
S
S
Department of Urology, Nara Medical University, Nara, Japan. ozn-kkr@nmu-gw.naramed-u.ac.jp
Yamaguchi
A
A
Mochizuki
H
H
Kawakami
T
T
Fujimoto
K
K
Otani
T
T
Yoshida
K
K
Ichinei
M
M
Yamashita
T
T
Hirao
Y
Y
D000368:Aged; D000726:Androgen Antagonists / Q000009:adverse effects* / Q000627:therapeutic use*; D002110:Caffeine; D056486:Chemical and Drug Induced Liver Injury; D019388:Cytochrome P-450 CYP1A2 / Q000494:pharmacology*; D005485:Flutamide / Q000009:adverse effects* / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010726:Phosphodiesterase Inhibitors; D011237:Predictive Value of Tests; D011471:Prostatic Neoplasms / Q000188:drug therapy*
D000726:Androgen Antagonists; D010726:Phosphodiesterase Inhibitors; D002110:Caffeine; D005485:Flutamide; D019388:Cytochrome P-450 CYP1A2