Effect of Ranitidine on Theophylline Metabolism in Healthy Koreans Living in China

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 (C_p) between 5 and 10 μg/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 (V_d), and half-life (t_1/2) were determined.

RESULTS:

Concurrent administration of ranitidine with theophylline did not significantly alter theophylline C_p, Cl, V_d, or t_1/2. 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.