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Impact of cimetidine on the pharmacokinetics of theophylline.

The effect of cimetidine on the pharmacokinetics of theophylline was evaluated. Twelve healthy men volunteers participated in this two-way crossover study. Six subjects were initially treated with theophylline (control), and six were treated with cimetidine and theophylline (cimetidine). Sixteen days after the start of the first phase, the subjects were crossed over. Aminophylline equivalent to 2 mg/kg theophylline was dissolved in 100 ml 5% dextrose injection and infused into an antecubital or forearm vein over a 20-minute period. Cimetidine was ingested in 300-mg doses every six hours beginning 48 hours before the theophylline infusion and continued until 48 hours after the infusion. Blood samples were collected periodically for 48 hours, and serum theophylline concentrations were determined by liquid chromatography. Theophylline concentration versus time data were computer fitted to a biexponential equation. Total theophylline clearance (CLtot), apparent volume of distribution (V), and elimination half-life (t 1/2 beta) were calculated. Semilogarithmic plots of theophylline disappearance showed a decrease during cimetidine treatment. Mean theophylline t 1/2 beta increased significantly during cimetidine treatment from 5.9 +/- 1.0 to 7.3 +/- 1.5 hr, and CLtot decreased significantly from 0.065 +/- 0.010 to 0.049 +/- 0.012 liter/hr/kg. Mean V was unchanged. Two subjects failed to exhibit decreased theophylline clearances, and theophylline clearance increased in another subject. Cimetidine was found to slow the clearance of theophylline and to extend its half-life. Daily doses of theophylline may require adjustment in patients requiring the coadministration of cimetidine. Cimetidine should be added with caution, and serum theophylline concentrations should be monitored accordingly.