Aims To examine the potential for alosetron to alter the pharmacokinetics of theophylline by inhibiting its metabolism, as suggested by in vitro and in vivo effects on CYP1A2 activity. Methods Ten healthy female volunteers received theophylline 200 mg twice daily alone for 8 days and with alosetron 1 mg twice daily for 15 days in this randomized, placebo-controlled, two-way-crossover study. Results Alosetron had no signi®cant effect on theophylline plasma concentrations (C max < 9 mg ml x1 , AUC< 90 mg ml x1 h) or oral formation clearance of three major metabolites produced via CYP1A2: 3-methylxanthine, 1-methylurate and 1,3-dimethylurate (5, 7 and 16 ml min x1 , respectively). Concomitant administration of alosetron and theophylline was well tolerated. Conclusions The absence of a clinical drug interaction involving inhibition of theophylline metabolism by alosetron was not predicted by in vitro and in vivo metabolic probe data.