The clearance of theophylline is increased during the initial period of tuberculosis treatment

Int J Tuberc Lung Dis. 2003 Jun;7(6):587-91.


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.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antitubercular Agents / administration & dosage
  • Antitubercular Agents / pharmacology*
  • Antitubercular Agents / therapeutic use*
  • Bronchodilator Agents / administration & dosage
  • Bronchodilator Agents / pharmacokinetics*
  • Bronchodilator Agents / therapeutic use
  • Drug Interactions
  • Drug Therapy, Combination
  • Ethambutol / administration & dosage
  • Ethambutol / pharmacology*
  • Ethambutol / therapeutic use*
  • Female
  • Humans
  • Isoniazid / administration & dosage
  • Isoniazid / pharmacology*
  • Isoniazid / therapeutic use*
  • Male
  • Middle Aged
  • Prospective Studies
  • Pyrazinamide / administration & dosage
  • Pyrazinamide / pharmacology*
  • Pyrazinamide / therapeutic use*
  • Rifampin / administration & dosage
  • Rifampin / pharmacology*
  • Rifampin / therapeutic use*
  • Theophylline / administration & dosage
  • Theophylline / pharmacokinetics*
  • Theophylline / therapeutic use
  • Time Factors
  • Tuberculosis, Pulmonary / drug therapy*


  • Antitubercular Agents
  • Bronchodilator Agents
  • Pyrazinamide
  • Ethambutol
  • Theophylline
  • Isoniazid
  • Rifampin