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Tuberc Respir Dis > Volume 47(4); 1999 > Article
Tuberculosis and Respiratory Diseases 1999;47(4):442-450.
DOI: https://doi.org/10.4046/trd.1999.47.4.442    Published online October 1, 1999.
Pharmacokinetic Profiles of Isoniazid and Rifampicin in Korean Tuberculosis Patients.
Seok Jin Ahn, Sang Joon Park, Kyeong Woo Kang, Gee Young Suh, Man Pyo Chung, Hojoong Kim, Jung Kwon, Chong H Rhee, Hee Soo Cha, Myoung Min Kim, Kyung Eob Choi
1Division of Pulmonology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. mpchung@smc.samsung.co.kr
2Clinical Pharmacology Research Center, Samsung Biomedical Research Institute, Seoul, Korea.
Abstract
BACKGROUND
Isoniazid(INH) and rifampicin(RFP) are the most effective anti-tuberculosis drugs which make the short-course chemotherapy possible. Although prescribed dosages of INH and RFP in Korea are different from those recommended by American Thoracic Society, there has been few study about pharmacokinetic profiles of INH and RFP in Korean patients who receive INH, RFP, ethambutol(EMB) and pyrazinamide(PZA) simultaneously. METHODS: Among the patients with active tuberculosis from Dec. 1997 to July 1998, we selected 17 patients. After an overnight fast, patients were given INH 300mg, RFP 450mg, EMB800mg and PZA 1500mg daily. Blood samples for the measurement of plasma INH(n=15) and RFP(n=17) level were drawn each at 0, 0.5, 1, 1.5, 2, 4, 6, 8 and 12hrs, and urine was also collected. INH and RFP level in the plasma and the urine were measured by high-performance liquid chromatography(HPLC). Pharmacokinetic parameters such as peak serum concentration(Cmax), time to reach to peak serum concentration(Tmax), half-life, elimination rate constant(Ke), total body clearance(CLtot), nonreanl clearance(CLnr), and renal clearance(CLr) were calculated. RESULTS: 1) Pharmacokinetic parameters of INH were as follows: Cmax; 7.63 +/- 3.20 micro gram /ml, Tmax; 0.73 +/- 0.22hr, half-life;2.12 +/- 0.84hrs, Ke;0.83 +/- 0.15hrs-1, CLtot;17.54 +/- 8.89L/hr, CLnr; 14.74 +/- 8.35L/hr, CLr; 2.79 +/- 1.31L/hr 2) Pharmacokinetic parameters of RFP were as follows : Cmax; 8.93 +/- 3.98 micro gram/ml, Tmax;1.76 +/- 1.13hrs, half-life;2.27 +/- 0.54hrs, Ke;0.32 +/- 0.08hrs-1, CLtot;14.63 +/- 6.60L/hr, CLr;1.04 +/- 1.55L/hr, CLnr;13.59 +/- 6.21L/hr. 3) While the correlation between body weight and Cmax of INH was not statistically significant (gamma=-0.514, p value >0.05), Cmax of RFP was significantly affected by body weight of the patients(gamma=-0.662, p value <0.01). CONCLUSION: In Korean patients with tuberculosis, 300mg of INH will be sufficient to reach the ideal peak blood level even in the patients over 50kg of body weight. However, 450mg of RFP will not be the adequate dose in the patients who weigh over 50~60kg.
Key Words: Isoniazid, Rifampicin, Pharmacokinetic, Korean


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