ABSTRACT
OBJECTIVE: To evaluate the effect of concurrent ranitidine therapy on theophylline metabolism in healthy Koreans. DESIGN: A 4-week, double-blind, randomized, placebo-controlled, crossover study. SETTING: The Clinical Research Unit, Department of Pharmaceutical Sciences, Yanbian Medical College, Yanji, China. SUBJECTS: Six young, healthy, nonsmoking Korean volunteers residing in China with no known factors that would alter theophylline metabolism. INTERVENTIONS: Subjects received extended-release oral theophylline at a constant dosage over 4 weeks to yield a serum concentration (Cp) between 5 and 10 micrograms/mL. Week 1 was the dosage titration phase. During week 2 subjects randomly received either ranitidine or a matching placebo. Week 3 was a washout phase, and during week 4 subjects were crossed over to receive either placebo or ranitidine. At the end of each treatment week, serum and urinary metabolite concentrations were measured. OUTCOME MEASURES: Theophylline serum concentrations and urinary concentrations of 1-methylxanthine, 1-methyluric acid, 3-methylxanthine, and 1,3-dimethyluric acid were measured. Estimates of clearance (Cl), volume of distribution (Vd), and half-life (t1/2) were determined. RESULTS: Concurrent administration of ranitidine with theophylline did not significantly alter theophylline Cp, Cl, Vd, or t1/2. Urinary concentrations of major theophylline metabolites also were not changed. CONCLUSIONS: Ranitidine does not significantly alter the metabolism of theophylline in healthy Koreans residing in China.
