Isoniazid, Rifampicin, Ethambutol, Pyrazinamide의 병용투여가 Theophylline의 약물동태에 미치는 영향

Effect of Combination Therapy of Isoniazid, Rifampicin, Ethambutol, and Pyrazinamide on Theophylline Pharmacokinetics

연구배경 : Theophylline은 간세포내 cytochrome P-450 계열의 효소에 의해 거의 90% 정도 대사되는데, isoniazid, rifampicin 등 항결핵제틀은 미소체 효소계(microsomal enzyme system)에 영향을 미치어 theophylline과의 병용투여시 theophylline 대사에 변화를 일으킬수 있다. 방 법 : INH, RFP, EMB 및 PZA의 병합 요법이 theophylline의 약물동태에 미치는 영향에 대하여 Bayesian 방법을 이용하여 평가하였다. Theophylline을 투여중인 환자를 대상으로 3군으로 나누어, Group I를 대조군으로 하였으며, Group II는 INH, RFP, EMB 및 PZA를 병용 투여하였고, Group III는 INH, RFP 및 EMB을 병용 투여하였다. 모든 대상환자는 비흡연자로 간기능 및 신기능 검사상 정상 범위였으며 theophylline의 약물동태에 영향을 줄 수 있을 만한 약제를 복용한 환자는 제외하였다. 결 과 : 정상 대조군과 실험군들을 비교시, theophylline 소실률은 Group II와 Group III 모두 유의하게 감소하였으며(p<0.001), theophylline 반감기 역시 Group II와 Group III 모두 유의하게 증가하였다 (p<0.001). 그러나 Group II와 Group III간의 theophylline 소실률 및 반감기는 차이가 없었다. 결 론 : 이상의 결과로 INH, RFP 및 EMB 등의 항결핵제와 theophylline 병용 투여시 theophylline 용량의 재조정이 필요할 것으로 사료된다.

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. Method : 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 I is control, Group II is treated with INH. RFP, EMB and PZA and Group III is treated with INH, RFP and EMB. All of them were ilon-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 II and Group III was significantly decreased(p<0.001), and half life in Group II and Group III showed significant elevation(p<0.001). However there were no significant differences in clearance and half life between the Group II and Group III. Conclusion : These results suggest that theophylline dose may be need of readjustment in concurrent medication of anti-tuberculous agents including INH, RFP, and EMB.