Pharmacokinetic interaction between theophylline and chloramphenicol in rats.

The effects of chloramphenicol, a potent enzyme inhibitor, on the pharmacokinetics of theophylline were investigated in Sprague-Dawley rats. Chloramphenicol treatment, 75 mg/day intravenously for 3 days, significantly (p less than 0.05) decreased the plasma clearance of theophylline by 31% with no apparent effects on the volume of distribution (0.97 liter/kg). The elimination half-life in chloramphenicol treated rats (N = 6) was 4.8 hr, significantly (p less than 0.05) longer than the corresponding half-life, 3.4 hr, in control rats (N = 6). It appears that chloramphenicol has a marked inhibitory effect on the activity of the cytochrome P-450-dependent mixed function oxidase liver microsome system responsible for the oxidation and demethylation of theophylline.