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.
RCT Entities:
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.
Authors: W Tassaneeyakul; D J Birkett; M E McManus; W Tassaneeyakul; M E Veronese; T Andersson; R H Tukey; J O Miners Journal: Biochem Pharmacol Date: 1994-05-18 Impact factor: 5.858
Authors: Kevin Koch; Corinne Campanella; Charlotte A Baidoo; Janet A Manzo; Vanessa Z Ameen; Kathryn E E Kersey Journal: Dig Dis Sci Date: 2004-08 Impact factor: 3.199