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  • Title: Cimetidine decreases theophylline clearance.
    Author: Jackson JE, Powell JR, Wandell M, Bentley J, Dorr R.
    Journal: Am Rev Respir Dis; 1981 Jun; 123(6):615-7. PubMed ID: 7023306.
    Abstract:
    This study tested the hypothesis that cimetidine decreases theophylline clearance. Aminophylline (6 mg/kg) was administered intravenously both before and after cimetidine treatment in 5 healthy adults. Cimetidine (300 mg) was administered orally every 6 h for 2 days before and 18 h after the aminophylline dose. Plasma samples were collected before and for 24 h after each aminophylline dose, and theophylline concentrations were determined by an enzyme-mediated immunoassay technique. Cimetidine significantly decreased theophylline clearance, mean decrease, 39% (3.85 +/- 0.27 L/h control versus 2.34 +/- 0.23 L/h with cimetidine treatment, p less than 0.002). The apparent volume of distribution was unchanged (p greater than 0.5), whereas the elimination rate constant was significantly decreased by a mean of 42% (control, 0.091 +/- 0.013 h-1 versus 0.053 +/- 0.007 h-1 with cimetidine treatment, p less than 0.005). This corresponded to an average increase in elimination half-life of 73% (range, 50 to 97%). Cimetidine probably slowed theophylline elimination by relatively nonspecific inhibition of the hepatic microsomal mono-oxygenase system. This effect may produce clinically significant changes in serum theophylline concentrations.
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