DONALD P. REITBERG, Pharm. D.; HAROLD BERNHARD, M.D.; JEROME J. SCHENTAG, Pharm. D.
Interaction between cimetidine and theophylline was studied in six male volunteers, who were randomly divided into two groups to eliminate temporal effects. The effect of cimetidine on theophylline elimination was immediate and progressed as cimetidine treatment was continued. Cimetidine prolonged theophylline half-life compared to that in control periods an average of 36.2% (range, 0 to 103%) on the first day of cimetidine exposure (p < 0.05). Theophylline clearance was decreased an average of 18.5% (range, 4.9% to 36%), whereas theophylline volume of distribution was unchanged by cimetidine. After 8 days of cimetidine treatment at the usually recommended dosage, theophylline half-life further increased to 64.3% (range, 9% to 128%) of control values, whereas clearance declined an average of 30% (range, 5% to 50%) (p < 0.01). Theophylline volume of distribution remained unchanged. Although cimetidine-theophylline interaction needs confirmation in a patient population, we advise caution when these agents are coadministered. Some adjustment in theophylline dosage may be needed in treated patients who are also given cimetidine, and these patients should be studied closely with theophylline serum concentration measurements and careful clinical assessments.
REITBERG DP, BERNHARD H, SCHENTAG JJ. Alteration of Theophylline Clearance and Half-life by Cimetidine in Normal Volunteers. Ann Intern Med. ;95:582–585. doi: 10.7326/0003-4819-95-5-582
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Published: Ann Intern Med. 1981;95(5):582-585.
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