CIMETIDINE DECREASES THEOPHYLLINE CLEARANCE

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Abstract
To determine if cimetidine decreases theophylline clearance aminophylline (6 mg/kg) was administered i.v. before and after cimetidine treatment in 5 healthy men. 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 concentration were determined by an enzyme-mediated immunoassay technique. Cimetidine significantly decreased theophylline clearance, mean decrease, 39% (3.85 .+-. 0.27 l/h control vs. 2.34 .+-. 0.23 l/h with cimetidine treatment P < 0.002). The apparent volume of distribution was unchanged P > 0.5; elimination rate constant was significantly decreased by a mean of 42% (control, 0.091 .+-. 0.013 h-1 vs. 0.053 .+-. 0.007 h-1 with cimetidine treatment P < 0.005). This corresponded to an average increase in elimination half-life of 73% (range, 50-97%). Cimetidine probably slowed theophylline elimination by relatively nonspecific inhibition of the hepatic microsomal mono-oxygenase system. Thsi effect may produce clinically significant changes in serum theophylline concentrations.