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


METHODS
Prospective, controlled clinical study.


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.
Ahn
H C
HC
Department of Pharmacy, Chonbuk National University Hospital, Chonju, Chonbuk, South Korea.
Lee
Y C
YC
D000328:Adult; D000368:Aged; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004977:Ethambutol / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007538:Isoniazid / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011718:Pyrazinamide / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D012293:Rifampin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D013806:Theophylline / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013997:Time Factors; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy*
D000995:Antitubercular Agents; D001993:Bronchodilator Agents; D011718:Pyrazinamide; D004977:Ethambutol; D013806:Theophylline; D007538:Isoniazid; D012293:Rifampin