Pharmacokinetic determination of relative potency of quinolone inhibition of caffeine disposition.

Quinolone is reported to interact with caffeine, often resulting in an increase both in the plasma half-life and AUC, a decrease in total plasma clearance, and little change in the absorption rate constant and maximum plasma level. These complex changes in the pharmacokinetics of caffeine were analyzed experimentally and from published reports in order to determine the nature of the interaction, which is thought to be due to inhibition of caffeine metabolism by quinolones. A simple pharmacokinetic model for the caffeine-quinolone interaction was developed, which provides a unified method for evaluation and comparison of the effect of quinolones on the disposition of caffeine. The model is applicable to other methylxanthines, such as theophylline. The relative potency of the interactions of quinolones with caffeine in humans has been established as enoxacin (100), pipemidic acid (29), ciprofloxacin (11), norfloxacin (9) and ofloxacin (0).