Correlation of plasma anti-tuberculosis drug levels with subsequent development of hepatotoxicity

Satyaraddi, A. and Velpandian, T. and Sharma, S. K. and Vishnubhatla, S. and Sharma, A. and Sirohiwal, A. and Makharia, G. K. and Sinha, S. and Biswas, A. and Singh, S. (2014) Correlation of plasma anti-tuberculosis drug levels with subsequent development of hepatotoxicity Int J Tuberc Lung Dis, 18 (2). pp. 188-195.

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Abstract

OBJECTIVES: To compare the free and total plasma drug concentrations of rifampicin (RMP), isoniazid and pyrazinamide in subjects with or without anti-tuberculosis drug-induced hepatotoxicity (DIH). METHODS: A total of 110 tuberculosis (TB) patients were administered daily anti-tuberculosis treatment and were prospectively followed for the development of DIH. Plasma drug levels were measured at 0, 1, 2 and 4 h on days 1, 7 and 14 of treatment. Plasma drug levels in 15 patients who developed DIH (cases) were compared with 95 patients who did not (controls). RESULTS: Female sex, body mass index < 17 kg/m(2) and baseline serum albumin < 4 g/dl predicted risk of DIH on univariate analyses. Free and total plasma RMP levels (Cmax and AUC0-4) on days 1, 7 and 14 were significantly higher in cases compared to controls and predicted development of DIH. Day 7 total RMP Cmax and AUC0-4 were higher in cases (mean 26.73, standard deviation [SD] 5.72 and 47.58, SD 33.10) than in controls (7.87, SD 10.95 and 14.01, SD 10.69, respectively). CONCLUSIONS: Plasma RMP levels were higher in cases than in controls and independently predicted subsequent development of DIH. The Cmax of Day 7 total RMP level (cut-off 12.50 mg/l) predicted subsequent development of DIH in 93.3% of the patients.

Item Type: Article
Uncontrolled Keywords: Anti-tuberculosis drugs; Plasma drug levels; Drug induced hepatotoxicity; Rifampicin
Subjects: Tuberculosis > Laboratory
Institutions: Zonal Task Force-State Task Force
Depositing User: Mr SANJAY SINGH
Date Deposited: 30 Jan 2014 11:38
Last Modified: 30 Jan 2014 11:38
URI: http://tbresearch.ntiindia.org.in/id/eprint/1570

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