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Effect of alosetron on theophylline pharmacokinetics
K M Koch1, B M Ricci, N S Hedayetullah
1Glaxo Wellcome Inc., Research Triangle Park, North Carolina 27709, USA.
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 significant effect on theophylline plasma concentrations (Cmax approximately 9 microg ml(-1), AUC approximately 90 microg ml(-1) 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(-1), 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.