Tuberc Respir Dis.  2006 Jan;60(1):44-48.

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

• Park IN
• Hong SB
• Oh YM
• Lim CM
• Lee SD
• Koh Y
• Kim WS
• Kim DS
• Kim WD
• Shim TS

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.

Keyword

Tuberculosis; Isoniazid; Acetylator phenotype; Treatmenrt

MeSH Terms

Body Weight
Chungcheongnam-do
Humans
Isoniazid*
Korea
Metabolism
Recurrence
Tuberculosis
Tuberculosis, Pulmonary*
Isoniazid

Reference

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. 167:603–662.

2. Joint Tuberculosis Committee of the British Thoracic Society. Chemotherapy and management of tuberculosis in the United Kingdom: recommendations 1998. Thorax. 1998. 53:536–548.

3. World Health Organization. Treatment of tuberculosis: guidelines for national tuberculosis programme. 2003. 3rd ed.

4. Peloquin CA. Pharmacology of the antimycobacterial drugs. Med Clin North Am. 1993. 77:1253–1262.

5. Korea Academy of Tuberculosis and Respiratory Disease. Guidelines for the management of pulmonary tuberculosis, 1997. Tuberc Respir Dis. 1997. 47:1447–1453.

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. 78:944–948.

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. 81:588–594.

10. Ellard GA. The potential clinical significance of the isoniazid acetylator phenotype in the teatment of pulmonary tuberculosis. Tubercle. 1984. 65:211–227.

11. Kergueris MF, Bourin M, Larousse C. Pharmacokinetics of isoniazid: influence of age. Eur J Clin Pharmacol. 1986. 30:335–340.

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. 44:479–492.

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. 47:442–450.

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. 276:1229–1235.

15. Iseman MD. Treatment of multidrug-resistant tuberculosis. N Engl J Med. 1993. 329:784–791.