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Memórias do Instituto Oswaldo Cruz
Fundação Oswaldo Cruz, Fiocruz
ISSN: 1678-8060 EISSN: 1678-8060
Vol. 110, No. 4, 2015, pp. 543-550
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Bioline Code: oc15069
Full paper language: English
Document type: Research Article
Document available free of charge
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Memórias do Instituto Oswaldo Cruz, Vol. 110, No. 4, 2015, pp. 543-550
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Using a single tablet daily to treat latent tuberculosis infection in Brazil: bioequivalence of two different isoniazid formulations (300 mg and 100 mg) demonstrated by a sensitive and rapid high-performance liquid chromatography-tandem mass spectrometry method in a randomised, crossover study
Daher, André; Pitta, Luciana; Santos, Tereza; Barreira, Draurio & Pinto, Douglas
Abstract
The recommended treatment for latent tuberculosis (TB) infection in adults is a daily dose of isoniazid (INH)
300 mg for six months. In Brazil, INH was formulated as 100 mg tablets. The treatment duration and the high pill
burden compromised patient adherence to the treatment. The Brazilian National Programme for Tuberculosis requested
a new 300 mg INH formulation. The aim of our study was to compare the bioavailability of the new INH
300 mg formulation and three 100 mg tablets of the reference formulation. We conducted a randomised, single dose,
open label, two-phase crossover bioequivalence study in 28 healthy human volunteers. The 90% confidence interval
for the INH maximum concentration of drug observed in plasma and area under the plasma concentration vs. time
curve from time zero to the last measurable concentration “time t” was 89.61-115.92 and 94.82-119.44, respectively.
The main limitation of our study was that neither adherence nor the safety profile of multiple doses was evaluated. To
determine the level of INH in human plasma, we developed and validated a sensitive, simple and rapid high-performance
liquid chromatography-tandem mass spectrometry method. Our results showed that the new formulation was
bioequivalent to the 100 mg reference product. This finding supports the use of a single 300 mg tablet daily strategy
to treat latent TB. This new formulation may increase patients’ adherence to the treatment and quality of life.
Keywords
latent tuberculosis; isoniazid; bioavailability; bioequivalence; HPLC-MS/MS method
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