Objective: To evaluate the effects of combined anti-tuberculosis treatment including isoniazid (INH), rifampicin (RMP), ethambutol (EMB) and pyrazinamide (PZA), on the pharmacokinetics of theophylline during the initial phase of treatment.
Design: Prospective, controlled clinical study.
Patients and methods: Twenty patients with pulmonary tuberculosis received 7.35 mg/kg/day of aminophylline intravenously combined with anti-tuberculosis agents. The first theophylline serum concentration was measured before administration of INH, RMP, EMB and PZA, and samples were obtained once daily for 6 consecutive days after initiation of treatment. All patients in this study were non-smokers with normal hepatic and renal function, and they were not given any other drugs that could affect the clearance of theophylline.
Results: The concentration and half-life of theophylline was decreased and its clearance was increased significantly at days 5-7 after administration of antituberculosis agents compared to before the therapy was started.
Conclusions: These results suggest that patients with asthma or chronic obstructive pulmonary disease administered combinations of anti-tuberculosis agents and theophylline during the initial phase of tuberculosis treatment should be monitored closely for changes in theophylline concentration, and that the dose of theophylline should be adjusted accordingly.