Pharmacokinetic and safety evaluation of the use of ciprofloxacin on an isoniazid-rifampicin regimen in rabbits

ABSTRACT The combination of isoniazid (INH), rifampicin (RMP) and pyrazinamide (PYR) is used in the treatment of tuberculosis. Although this treatment is effective in most clinical cases, the side‐effects and the development of mycobacterium resistance have hindered its success. There is evidence th...

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Published in:Biopharmaceutics & drug disposition 2012-12, Vol.33 (9), p.501-509
Main Authors: Padilha, Elias Carvalho, Pires, Rodrigo Vieira, Filho, Marco Antonio Ferraz Nogueira, de Pontes Machado, Diego Vinicius, Baldan, Helen Mariana, Davanço, Marcelo Gomes, Campos, Michel Leandro, Brunetti, Iguatemy Lourenço, Peccinini, Rosângela Gonçalves
Format: Article
Language:English
Subjects:
Alanine Transaminase - blood
Alkaline Phosphatase - blood
Animals
Antibiotics, Antitubercular - administration & dosage
Antibiotics, Antitubercular - blood
Antibiotics, Antitubercular - pharmacokinetics
Aspartate Aminotransferases - blood
Bilirubin - blood
ciprofloxacin
Ciprofloxacin - administration & dosage
Ciprofloxacin - pharmacokinetics
Drug Combinations
Drug therapy
hepatotoxicity
isoniazid
Isoniazid - administration & dosage
Isoniazid - blood
Isoniazid - pharmacokinetics
Male
preclinical pharmacokinetics
Rabbits
Rifampin - administration & dosage
Rifampin - pharmacokinetics
tuberculosis
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Summary:ABSTRACT The combination of isoniazid (INH), rifampicin (RMP) and pyrazinamide (PYR) is used in the treatment of tuberculosis. Although this treatment is effective in most clinical cases, the side‐effects and the development of mycobacterium resistance have hindered its success. There is evidence that the combination of INH, RMP and ciprofloxacin (CIPRO) is useful in the treatment of tuberculosis. However, the influence of this drug combination on the hepatotoxicity of INH is unknown. In this study, the safety of combined INH, RMP and CIPRO was evaluated. Male albino rabbits (n = 20) were divided into four groups and subjected to multiple oral doses for 7 days according to the following treatments: water (group 1); 50 mg/kg INH (group 2); 50 mg/kg INH + 100 mg/kg RMP (group 3) and 50 mg/kg INH + 100 mg/kg RMP + 50 mg/kg CIPRO (group 4). Blood samples were taken before and after treatments for the determination of ALT, AST, ALP and bilirubin to assess hepatotoxicity. For pharmacokinetic analysis, serial blood samples were collected over 24 h on day 7 of treatment. Plasma concentrations of INH and acetylisoniazid (AcINH) were determined by HPLC. Biochemical parameters did not show any statistically significant differences between the groups that received the drug combinations. The pharmacokinetic profile of INH was also similar for both groups of combinations. These findings allow us to infer that the inclusion of CIPRO did not increase the risk of hepatotoxicity when compared with the classic combination of INH and RMP. Copyright © 2012 John Wiley & Sons, Ltd.
ISSN:0142-2782
1099-081X
DOI:10.1002/bdd.1817