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Bioavailability of rifampicin following concomitant administration of ethambutol or isoniazid or pyrazinamide or a combination of the three drugs

Immanuel, Chandra and Gurumurthy, Prema and Ramachandran, Geetha and Venkatesan, P and Chandrasekaran, V and Prabhakar, R (2003) Bioavailability of rifampicin following concomitant administration of ethambutol or isoniazid or pyrazinamide or a combination of the three drugs. Indian Journal of Medical Research, 118 (Sep). pp. 109-114. ISSN 0971-5916

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Abstract

Background & Objectives: Poor bioavailability of rifampicin (R) in combination with other anti-tuberculosis drugs such as isoniazid (H), pyrazinamide (Z), and ethambutol (E) is a subject of much concern for the last few decades. This could be due to an interaction between R and other drugs. An investigation was therefore undertaken to examine the bioavailability of R in the presence of H, Z and E or a combination of the three drugs. Methods: The study included eight healthy volunteers, each being investigated on four occasions at weekly intervals once with R alone and with three of the four combinations on the three remaining occasions. A partially balanced incomplete block design was employed and the allocation of R or the drug combinations was random. Plasma concentrations of R at intervals upto 12 h were determined by microbiological assay using Staphylococcus aureus as the test organism. The proportion (%) dose of R as R plus desacetyl R (DR) in urine excreted over the periods 0-8 and 8-12 h was also determined. Bioavailability was expressed as an index (BI) of area under time concentration curve (AUC) calculated from the plasma concentrations or proportion of dose of R excreted as R plus DR in urine with the combinations to that with R alone. Results: The bioavailability indices based on AUC were 0.96 with RE, 0.76 with RH, 1.08 with RZ and 0.65 with REHZ. The indices based on urine estimations (0-8 h) were similar, the values being 0.94, 0.84, 0.94 and 0.75, respectively. A second investigation revealed that the decrease of bioavailability of R with H was not due to the excipients present in H tablets. Interpretation & conclusion: Isoniazid alone or in combination with E and Z reduces the bioavailability of R. Urinary excretion data offer a simple and non invasive method for the assessment of bioavailability of R.

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Item Type: Article
Uncontrolled Keywords: Bioavailability, rifampicin, treatment, tuberculosis, urinary excretion
Subjects: Tuberculosis > Laboratory Research > Biochemical,Clinical and Pharmacological
Divisions: Basic Science Research > Biochemistry and Pharmacology
Depositing User: Dr. Rathinasabapati R
Date Deposited: 12 Nov 2013 09:06
Last Modified: 09 Mar 2016 10:53
URI: http://eprints.nirt.res.in/id/eprint/596

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