Tuberculosis and Respiratory Diseases

The Korean Academy of Tuberculosis and Respiratory Diseases (대한결핵및호흡기학회)
권호 표지

Comparison of Effectiveness and Adverse Reactions between Isoniazid 300 mg and 400 mg in Korean Patients with Pulmonary Tuberculosis

한국인 폐결핵 환자의 표준치료에서 Isoniazid 300 mg 및 400 mg의 치료 효과와 부작용의 비교

  • Park, I-Nae (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Hong, Sang-Bum (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Oh, Yeon-Mok (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Lim, Chae-Man (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Lee, Sang Do (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Koh, Younsuck (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Kim, Woo Sung (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Kim, Dong Soon (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Kim, Won Dong (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Shim, Tae Sun (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center)
  • 박이내 (울산대학교 의과대학 서울아산병원 호흡기내과) ;
  • 홍상범 (울산대학교 의과대학 서울아산병원 호흡기내과) ;
  • 오연목 (울산대학교 의과대학 서울아산병원 호흡기내과) ;
  • 임채만 (울산대학교 의과대학 서울아산병원 호흡기내과) ;
  • 이상도 (울산대학교 의과대학 서울아산병원 호흡기내과) ;
  • 고윤석 (울산대학교 의과대학 서울아산병원 호흡기내과) ;
  • 김우성 (울산대학교 의과대학 서울아산병원 호흡기내과) ;
  • 김동순 (울산대학교 의과대학 서울아산병원 호흡기내과) ;
  • 김원동 (울산대학교 의과대학 서울아산병원 호흡기내과) ;
  • 심태선 (울산대학교 의과대학 서울아산병원 호흡기내과)
  • Received : 2005.11.02
  • Accepted : 2005.12.19
  • Published : 2006.01.30
Download PDF
⟨ Previous Next ⟩

Abstract

Background : Isoniazid (INH) is one of the most effective anti-tuberculosis (TB) drugs. In Korea, the dose of INH normally used in patients over 50 kg is 400 mg/day, which differs from the dose recommended by other countries. Indeed, the metabolism of INH shows ethnic variations, and Koreans are predominantly rapid acetylators. However, two reports suggested 300 mg of INH might be sufficient to reach an ideal peak level in Korean patients over 50 kg. Therefore, the aim of this study was to compare the effectiveness and adverse reactions between INH 300 mg and 400 mg in Korean TB patients. Method : Patients who were culture-positive, susceptible to all 1st-line drugs, initially on HREZ, and weighed over 50 kg were selected from patients with pulmonary TB between April 2003 and March 2005. The treatment results and adverse reactions in the INH 300 mg and 400 mg group were compared. Since April 2004, most TB patients at Asan Medical Center were administered INH 300 mg irrespective of the body weight. Results : The study included 123 patients in the 300 mg INH group and 128 in the 400 mg INH group. There were no significant differences between the groups in terms of age, gender, weight, history of TB treatment, initial smear strength, and frequency of cavitary lesions. There was no difference in the treatment duration between the groups. One hundred eleven (90%) patients in the INH 300 mg group and 102 (80%) in the INH 400 mg group completed treatment (p>0.05). There were no differences in the frequency of modification of the initial regimen between groups due to any adverse reactions (300 mg : 9.0%, 400 mg : 13.7%) and hepatotoxicity (300 mg : 2.7% ; 400 mg : 7.8%). Conclusion : Considering treatment results and adverse reactions of two groups, 300mg of INH may be sufficient for treating Korean TB patients. Further studies comparing the frequency of relapse will be needed.

연구배경 : Isoniazid (INH)에 관한 국내 폐결핵 진료지침은 외국의 지침들(300 mg/일)과 달리 체중이 50kg 이상인 경우 400 mg/일을 권장량으로 제시하고 있으나 근거가 없는 실정이다. 따라서 국내에서 1차 4제요법 치료시 INH 300 mg/일과 400 mg/일 처방에 따른 차이를 확인하기 위해 본 연구를 시행하였다. 방 법 : 폐결핵으로 진단받고 표준 4제치료를 시행한 환자 중 50kg 이상이고 모든 1차약제 감수성이 확인된 환자를 INH 300 mg/일과 400 mg/일 군으로 나누어 비교하였다. 결 과 : 2003년 4월부터 2005년 3월까지 상기 조건을 만족하는 환자 중 INH 300 mg을 사용한 군(300군)은 123명, 400 mg을 사용한 군은 128명(400군)이었다. 나이, 남녀비, 체중, 결핵치료력, AFB 도말 양성률, 공동병소 동반율에서 300군 및 400군 간 유의한 차이는 없었다. 300군 및 400군에서 치료 완료율은 90%:80%였고, 전체 부작용에 의한 약제 변경률은 9.0%:13.7%, 간독성에 의한 약제 변경률은 2.7%:7.8%로 유의한 차이가 없었다. 추적 관찰 기간이 짧아 재발률은 분석되지 않았다. 결 론 : INH 300군과 400군 사이에 치료성적 및 약제 부작용면에서 차이가 없어서 50kg 이상의 결핵환자의 표 준처방시 INH 300mg이 유용하다고 사료되나 향후 재발률의 비교 연구가 필요하다.

Keywords

References

  1. Blumberg HM, Burman WJ, Chaisson RE, Daley CL, Etkind SC, Friedman LN, et al. American Thoracic Society/Centers for Disease Control and Prevention/ Infectious Diseases Society of America: treatment of tuberculosis. Am J Respir Crit Care Med 2003;167:603-62 https://doi.org/10.1164/rccm.167.4.603
  2. Joint Tuberculosis Committee of the British Thoracic Society. Chemotherapy and management of tuberculosis in the United Kingdom: recommendations 1998. Thorax 1998;53:536-48 https://doi.org/10.1136/thx.53.7.536
  3. World Health Organization. Treatment of tuberculosis: guidelines for national tuberculosis programme. 3rd ed. 2003
  4. Peloquin CA. Pharmacology of the antimycobacterial drugs. Med Clin North Am 1993;77:1253-62 https://doi.org/10.1016/S0025-7125(16)30191-2
  5. Korea Academy of Tuberculosis and Respiratory Disease. Guidelines for the management of pulmonary tuberculosis, 1997. Tuberc Respir Dis 1997;47:1447- 53
  6. Korea Center for Disease Control and Prevention. Guidelines for the management of tuberculosis 2004
  7. Lee HS, Song HS, Lee HK, Kim KH, Chung HS, Kim CK, et al. Isoniazid metabolism and its clinical implications in Koreans. Tuberc Respir Dis 1962;12:22-37
  8. Harris HW, Knight PA, Selin MJ. Comparisons of isoniazid concentrations in the blood of people of Japanes and European descent. Am Rev Tuberc 1958;78: 944-8
  9. Armstrong AR, Peart HE. A comparison between the behavior of the Eskimos and non-Eskimos to the administration of INH. Am Rev Resp Dis 1960;81:588-94
  10. Ellard GA. The potential clinical significance of the isoniazid acetylator phenotype in the teatment of pulmonary tuberculosis. Tubercle 1984;65:211-27 https://doi.org/10.1016/0041-3879(84)90079-5
  11. Kergueris MF, Bourin M, Larousse C. Pharmacokinetics of isoniazid: influence of age. Eur J Clin Pharmacol 1986;30:335-40 https://doi.org/10.1007/BF00541539
  12. Chung MP, Kim HC, Suh GY, Park JW, Kim H, Kwon OJ, et al. Pharmacokinetic study of isoniazid and rifampicin in healthy Korean volunteers. Tuberc Respir Dis 1997;44:479-92 https://doi.org/10.4046/trd.1997.44.3.479
  13. Ahn SJ, Park SJ, Kang KW, Suh GY, Chung MP, Kim H, et al. Pharmacokinetic profiles of isoniazid and rifampicin in Korean tuberculosis patients. Tuberc Respir Dis 1999;47:442-50 https://doi.org/10.4046/trd.1999.47.4.442
  14. Frieden TR, Sherman LF, Maw KL, Fujiwara PI, Crawford JT, Nivin B, et al. A multi-institutional outbreak of highly drug-resistant tuberculosis: epidemiology and clinical outcomes. JAMA 1996;276:1229-35 https://doi.org/10.1001/jama.276.15.1229
  15. Iseman MD. Treatment of multidrug-resistant tuberculosis. N Engl J Med 1993;329:784-91 https://doi.org/10.1056/NEJM199309093291108