Increasing serum transaminase is not associated with the serum isoniazid and rifampicin levels in tuberculosis patients treated with fixed-dose combination antituberculosis in Yogyakarta

Abstract

Tuberculosis (TB) remains a major health problem in the world. Isoniazid (INH) and rifampicin are first-line antituberculosis that can cause hepatotoxicity characterized by an increase of serum transaminase level. Previous study showed the increase in transaminase level of TB patients due to INH and rifampicin. However, it did not explain about its correlation with the drugs concentration. The aim of this study was to evaluate the relationship between the increase of serum INH and rifampicin concentrations and the increase of serum transaminase level in TB patients. This was a cross sectional study involving 31 TB patients who underwent intensive phase of treatment with fixed-dose combination antitubercuosis therapy (FDC-ATT) in Yogyakarta. Serum transaminase levels i.e. AST and ALT before and at the end of the intensive phase of treatment were determined by an automatic chemical analyzer. Serum INH and rifampicin concentrations at the end of the intensive phase of treatment were measured by HPLC. t- test, Mann Whitney, Fisher and Spearman tests were used to analyze the data. Mean of INH and rifampicin concentrations were 2.72 ± 0.46 µg/mL and 4.12 ± 0.42 µg/mL, respectively. Mean of INH and rifampicin concentrations of TB patients with high AST level (5.03 ± 4.14 µg/mL and 8.52 ± 3.06 µg/mL) tended to be higher than those with normal AST level (2.47 ± 0.27 µg/mL and 3.64 ± 0.32 µg/mL). However, they were not significantly difference (p>0.05). Furthermore, mean of INH and rifampicin concentrations of TB patients with high ALT level (7.07 ± 6.24 µg/mL and 10.67 ± 3.76 µg/mL) also tended to be higher than those with normal AST level (2.42 ± 0.26 µg/mL and 3.66 ± 0.30 µg/mL). However, they were not also significantly difference (p>0.05). In conclusion, there are no correlation between INH and rifampicin concentrations and the increase of transaminase level in TB patients after intensive phase of treatment.