Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.17.3.2 (xanthine oxidase)
 8,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Terbinafine is an allylamine antifungal agent used for the treatment of onychomycosis. It has previously been reported to interact with caffeine and is metabolized in part by the cytochrome P450 systems. This open-label, randomized, crossover study was conducted to examine the effect of terbinafine on the activity of cytochrome P450 1A2 (CYP1A2), N-acetyltransferase (NAT-2), and xanthine oxidase (XO). Twelve healthy nonsmoking adult volunteers were enrolled. Each received single doses of caffeine (100 mg), and urine was collected for a 16-hour period with and without multiple-dose oral administration of terbinafine (250 mg daily for 3 days). Study periods were separated by a 4-week washout period. Urinary caffeine metabolite ratios were used to assess CYP1A2, NAT-2 and XO activity. Comparison of mean metabolic ratios for treatment with and without terbinafine indicated that terbinafine did not appear to alter the activity of CYP1A2, NAT-2, or XO, all of which regulate the biotransformation of caffeine.
 ...
PMID:Absence of effect of terbinafine on the activity of CYP1A2, NAT-2, and xanthine oxidase. 960 54

We completed a phase I trial of indole-3-carbinol (I3C) in 17 women (1 postmenopausal and 16 premenopausal) from a high-risk breast cancer cohort. After a 4-week placebo run-in period, subjects ingested 400 mg I3C daily for 4 weeks followed by a 4-week period of 800 mg I3C daily. These chronic doses were tolerated well by all subjects. Hormonal variables were measured near the end of the placebo and dosing periods, including determination of the urinary 2-hydroxyestrone/16alpha-hydroxyestrone ratio. Measurements were made during the follicular phase for premenopausal women. Serum estradiol, progesterone, luteinizing hormone, follicle-stimulating hormone, and sex hormone binding globulin showed no significant changes in response to I3C. Caffeine was used to probe for cytochrome P450 1A2 (CYP1A2), N-acetyltransferase-2 (NAT-2), and xanthine oxidase. Comparing the results from the placebo and the 800 mg daily dose period, CYP1A2 was elevated by I3C in 94% of the subjects, with a mean increase of 4.1-fold. In subjects with high NAT-2 activities, these were decreased to 11% by I3C administration but not altered if NAT-2 activity was initially low. Xanthine oxidase was not affected. Lymphocyte glutathione S-transferase activity was increased by 69% in response to I3C. The apparent induction of CYP1A2 was mirrored by a 66% increase in the urinary 2-hydroxyestrone/16alpha-hydroxyestrone ratio in response to I3C. The maximal increase was observed with the 400 mg daily dose of I3C, with no further increase found at 800 mg daily. If the ratio of hydroxylated estrone metabolites is a biomarker for chemoprevention, as suggested, then 400 mg I3C daily will elicit a maximal protective effect.
 ...
PMID:A phase I study of indole-3-carbinol in women: tolerability and effects. 1610 43