The effect of rifampin on theophylline kinetics.

The effect of rifampin on the pharmacokinetics of theophylline was studied in ten healthy nonsmoking men (age, 23-42 years). Each subject received 5.9-6.8 mg/kg of aminophylline intravenously over 20 minutes before and at the end of two weeks of oral rifampin therapy (600 mg/d). Theophylline serum concentrations were measured serially over the 24 hours following each aminophylline infusion. In every subject, rifampin caused an increase in total clearance (from 0.88 +/- 0.21 to 1.21 +/- 0.29 mL/min/kg) and terminal elimination rate constant (from 0.104 +/- 0.023 to 0.148 +/- 0.030 hr-1) and a decrease in the area under the theophylline concentration-time curve (from 104 +/- 29 to 76 +/- 19 hr-mg/L) and half-life of theophylline (from 7.0 +/- 1.7 to 4.8 +/- 0.9 hr). All of these changes were significant (P less than .02, Wilcoxon matched-pair, signed-rank, two-tailed test). The apparent volume of distribution of theophylline did not consistently change following rifampin administration (mean change, -4%; range, -18(-)+20%, P greater than .20). Patients should be monitored for signs of decreased theophylline efficacy when rifampin is added, or of increased theophylline toxicity when rifampin is discontinued from maintainance therapy.