Absence of Effect of Terbinafine on the Activity of CYP1A2, NAT-2, and Xanthine Oxidase

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.