Abstract
Various drugs have been used for the treatment of antitubercular treatment. Such drugs may often lead to hepatotoxicity. Aim: To Access the pharmacokinetic profile of rifampicin and isoniazid and metabolites of isoniazid viz. Mono Acetyl Hydrazine (MAH) and Diacetyl Hydrazine (DAH) in patients of pulmonary tuberculosis which served as control group and in patients of Antitubercular Drugs (ATD) induce hepatotoxicity. Materials and methods: Ten patients of pulmonary tuberculosis already receiving ATD for at least last four weeks and had no clinical hepatotoxicity and ten patients of pulmonary tuberculosis suffering from ATD induced hepatotoxicity were included. Liver Function Test Serum bilirubin, SGOT, SGPT, Serum Alkaline phosphatase, Prothrombin time, HbsAg, IgM anti HBc for hepatitis B, blood urea and serum creatinine were investigated. Results: Patients suffering from ATD induced hepatotoxicity have shown increased peak serum Conc. t1/2 and decrease in serum clearance of INH and increase in peak serum concentration, AUC & decrease clearance of RMP indicating that there was delayed elimination of both the drugs (RMP, INH) which may further cause hepatotoxicity. Conclusion: It was concluded that in patients of liver derangement low dose of INH and rifampicin should be given and plasma levels of MAH may act as an indicator to predict hepatotoxicity in patients receiving antitubercular treatment.
Highlights
It was concluded that in patients of liver derangement low dose of INH and rifampicin should be given and plasma levels of Mono Acetyl Hydrazine (MAH) may act as an indicator to predict hepatotoxicity in patients receiving antitubercular treatment
The development of highly effective short course chemotherapy for the treatment of pulmonary tuberculosis was made possible by the introduction of combined isoniazid and rifampicin containing regimens
The present study was undertaken to assess the pharmacokinetic profile of rifampicin, INH and metabolites INH viz. MAH and Diacetyl Hydrazine (DAH) in patients of pulmonary tuberculosis which served as control group and in patients of Antitubercular Drugs (ATD) induce hepatotoxicity
Summary
The development of highly effective short course chemotherapy for the treatment of pulmonary tuberculosis was made possible by the introduction of combined isoniazid and rifampicin containing regimens. Serious side effects attributed to isoniazid or rifampicin treatment is rare [1]. One of the most important toxic manifestations is clinical hepatitis with Jaundice which occurs with an incidence of about 1-3% and the incidence of hepatotoxicity increases to 8-10% when isoniazid is given along with rifampicin [2]. The clinical features of a few patients suggest a hypersensitivity reaction to the drug [3]. Studies in animals have shown that one of the metabolite of isoniazid acetyl hydrazine is a potent hepatotoxic [5]. Acetyl hydrazine requires metabolic activation by the hepatotoxygenase system to a reactive intermediate that covalently binds to apparently vital hepatic macromolecules to exert its toxic effects
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