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

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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/m2 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.

Keywords: anti-tuberculosis drugs; drug induced hepatotoxicity; plasma drug levels; rifampicin

Document Type: Research Article

DOI: http://dx.doi.org/10.5588/ijtld.13.0128

Affiliations: 1: Department of Medicine, All India Institute of Medical Sciences, New Delhi, India 2: Department of Ocular Pharmacology and Pharmacy, Dr Rajender Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India 3: Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India 4: Medical University, Pleven, Bulgaria 5: Department of Ophthalmology, Dr Rajender Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India 6: Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India 7: Department of Laboratory Medicine, All India Institute of Medical Sciences, New Delhi, India

Publication date: February 1, 2014

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  • The International Journal of Tuberculosis and Lung Disease publishes articles on all aspects of lung health, including public health-related issues such as training programmes, cost-benefit analysis, legislation, epidemiology, intervention studies and health systems research. The IJTLD is dedicated to the continuing education of physicians and health personnel and the dissemination of information on tuberculosis and lung health world-wide.

    Certain IJTLD articles are selected for translation into French, Spanish, Chinese or Russian. They are available on the Union website

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