Effect of ranitidine on theophylline metabolism in healthy Koreans living in China.
OBJECTIVE
To evaluate the effect of concurrent ranitidine therapy on theophylline metabolism in healthy Koreans.


METHODS
A 4-week, double-blind, randomized, placebo-controlled, crossover study.


METHODS
The Clinical Research Unit, Department of Pharmaceutical Sciences, Yanbian Medical College, Yanji, China.


METHODS
Six young, healthy, nonsmoking Korean volunteers residing in China with no known factors that would alter theophylline metabolism.


METHODS
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.


METHODS
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.
Kehoe
W A
WA
Clinical Pharmacy, University of the Pacific, Stockton, CA 95211, USA.
Sands
C D
CD
Long
L F
LF
Lan
H H
HH
Harralson
A F
AF
Shin
H T
HT
Jones
D W
DW
D000293:Adolescent; D000328:Adult; D001711:Biotransformation; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D002681:China; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D004347:Drug Interactions; D006635:Histamine H2 Antagonists / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D007723:Korea / Q000208:ethnology; D008875:Middle Aged; D011899:Ranitidine / Q000009:adverse effects / Q000494:pharmacology*; D013806:Theophylline / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*
D001993:Bronchodilator Agents; D003692:Delayed-Action Preparations; D006635:Histamine H2 Antagonists; D011899:Ranitidine; D013806:Theophylline