Effect of alosetron on theophylline pharmacokinetics

Aims To examine the potential for alosetron to alter the pharmacokinetics o f theophylline by inhibiting its metabolism, as suggested by in vitro and i n view effects on CYP1A2 activity. Methods Ten healthy female volunteers received theophylline 200 mg twice da ily alone for 8 days and with alosetron 1 mg twice daily for 15 days in thi s randomized. placebo-controlled, two-way-crossover study. Results Alosetron had no significant effect on theophylline plasma concentr ations (C-max approximate to 9 mug ml(-1) AUC approximate to 90 mug ml(-1) h) or oral formation clearance of three major metabolites produced via CYP1 A2: 3-methylxanthine, 1-methylurate and 1,3-dimethylurate (5, 7 and 16 ml m in(-1), respectively). Concomitant administration of alosetron and theophyl line was well tolerated. Conclusions The absence of a clinical drug interaction involving inhibition of theophylline metabolism by alosetron,vas not predicted by in vitro and in vivo metabolic probe data.