The effects of cimetidine on theophylline pharmacokinetics at steady state.

The effects of cimetidine on the pharmacokinetics of theophylline were studied in seven healthy subjects at steady state after oral dosing. Aminophylline (200 mg) was administered every six hours for three days (A), then aminophylline (200 mg) and cimetidine (300 mg) were administered every six hours for seven days (A-C). Multiple serum theophylline determinations were made after the last dose on each regimen using an enzyme immunoassay. Cimetidine decreased the apparent total body clearance of theophylline an average of 29 percent (range: 18-47 percent) from 39.5 +/- 11.7 to 28.1 +/- 3.4 ml/hr/kg (p less than 0.02). There was no significant change in the volume of distribution; however, the terminal half-life increased from 7.3 +/- 1.5 to 10.1 +/- 2.1 hr (p less than 0.01) during A and A-C, respectively. The increase in the average steady state serum theophylline concentration of 34 percent (range: 23-87 percent) observed in our subjects may have important clinical implications.