iwan Dwiprahasto
Department of Pharmacology and Therapy, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia

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The influence of acetylation status of tuberculosis patients on the isoniazid serum concentrations and sputum conversion after intensive phase therapy Dwi Indria Anggraini; Erna Kristin; iwan Dwiprahasto
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 50, No 1 (2018)
Publisher : Journal of the Medical Sciences (Berkala Ilmu Kedokteran)

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (429.047 KB) | DOI: 10.19106/JMedSci005001201807

Abstract

Isoniazid (INH), one of the major antituberculosis drugs, is metabolized by acetylation. Previously study proved the significant differences of serum INH concentration between subject with fast and slow acetylation status. However, the correlation of acetylation status with treatment outcome after fixed-dose combination antituberculosis therapy (FDC-ATT) was not explained. The aim of this study was to evaluate the influence of acetylation status on the treatment outcome and the serum INH concentrations in the adult tuberculosis patients underwent FDC-ATT. A cross sectional study was carried out on 31 tuberculosis patients. Acetylation status was measured by spectrophotometer and serum INH concentration was measured by high performance liquid chromatography (HPLC). Sputum conversion assay was conducted by Ziehl Nelsen method. t-Test, chi square, Mann-Whitney, and Fisherman were used to analyze the data. The proportion of the fast acetylator was 61.3%, whereas the slow acetylator was 38.7%. The proportion of success and failure sputum conversion were 83.9% and 16.1%, respectively. The mean serum INH concentration in the fast acetylator groups (1.52 ± 0.15 μg/mL) was significantly lower than that in the slow acetylator groups (3.84 ± 0.35 μg/mL). The failure conversion risk of the fast acetylator group was about two folds higher than the slow acetylator group, although it was not significantly different (RR=2.53; 95% CI=0.32-20.00; p>0.05). Moreover, the mean serum INH concentration in success (2.46 ± 0.31 μg/mL) and failure (1.89 ± 0.20 μg/mL) sputum conversion was not significantly different (p>0.05). In conclusion, the acetylation status does not influence the sputum conversion in adult tuberculosis patients after FDC-ATT although the serum INH concentration on slow acetylation status is higher than that fast acetylation status. 
Increasing Serum Transaminase and The Relation with The Serum Concentration of Isoniazid and Rifampicin of Tuberculosis Patients which Given Antituberculosis Fixed Dose Combination in Yogyakarta Ratih Puspita Febrinasari; Erna Kristin; Iwan Dwiprahasto
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) Vol 47, No 4 (2015)
Publisher : Journal of the Medical Sciences (Berkala Ilmu Kedokteran)

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (316.476 KB) | DOI: 10.19106/JMedSci004704201504

Abstract

ABSTRACT Tuberculosis is still a major health problem in Indonesia. Isoniazid and rifampicin are major antituberculosis drugs. These two drugs have been known to cause hepatotoxicity which is characterized by an increase of serum transaminase concentration. Previous study proved the increase of hepatotoxicity due to isoniazid and rifampicin but did not explain about the correlation with the drugs concentration. The aim of this study is to know the relation between increasing serum transaminase and the serum concentration of  isoniazid and rifampicin of tuberculosis patients which given antituberculosis fixed dose combination in Yogyakarta. We carried out a cross sectional study involving 31 TB patients who received antituberculosis fixed dose combination containing isoniazid and rifampicin. Serum transaminase was measured with an automatic chemical analyzer. Isoniazid and rifampicin concentration was measured by using HPLC. We used t- test, Mann Whitney, Fisher and Spearman to analyze the data. There is no correlation between mean isoniazid concentration with high (7,07±6,24mg/ml) and normal ALT (2,42±0,26mg/ml)  (p>0,05). There is no correlation between mean isoniazid concentration with high (5,03+4,14 mg/ml) and normal AST (p>0,05). There is no correlation between mean rifampicin concentration with high (10,67+3,76 mg/ml) and normal ALT (3,66+0,30 mg/ml) (p>0,05). There is no correlation between mean rifampicin concentration with high (8,52+3,06 mg/ml) and normal AST (3,64+0,32 mg/ml) (p>0,05). Mean of rifampicin concentration in this study are low (4, 12+0,46 mg/ml). So the conclusion that there are no correlation between isoniazid serum concentration with an increase of serum transaminase and no correlation between rifampicin serum concentration with an increase of serum transaminase.