Effect of Combination Therapy of Isoniazid, Rifampicin, Ethambutol, and Pyazinamide on Theophylline Pharmacokinetics / 결핵

ABSTRACT

BACKGROUND: Since up to 90% of a theophylline dose is biotransformed, probably by interaction with one or more the variants of the cytochrome P-450 drug metabolism system, anti-tuberculosis agents including drugs influencing microsomal enzyme systems, such as isoniazid and rifampicin, may be affect the elimination of theophylline. METHODS: The effect of combination therapy with isoniazid(INH), rifampicin(RFP), ethambutol(EMB) and pyrazinamide(PZA) on the pharmacokinetics of theophylline was evaluated by a computer program using Bayesian method. Three group were divided as follows. Group lis control, Group II is treated with INH, RFP, EMB and PZA and Group lll is treated with INH, RFP and EMB. All of them were non-smoker who were normal in liver and renal functions, and not administered drugs affecting on the clearance of theophylline with exception of anti-tuberculous agents. RESULTS: When it compared control with test groups, the clearance of theophylline in Group ll and Group lll was significantly decreased(p<0.001), and half life in Group ll and Group lll showed significant elevation(p<0.001). However there were no significant differences in clearance and half life between the Group ll and Group lll. CONCLUSION: These results suggest that theophylline dose may be need of readjustment in concurrent medica fion of anti-tuberculous agents including INH, RFP, and EMB.