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

Autor(es)

Padilha, Elias Carvalho ^[1] ; Pires, Rodrigo Vieira ^[1] ; Ferraz Nogueira Filho, Marco Antonio ^[1] ; de Pontes Machado, Diego Vinicius ^[1] ; Baldan, Helen Mariana ^[1] ; Davanco, Marcelo Gomes ^[1] ; Campos, Michel Leandro ^[1] ; Brunetti, Iguatemy Lourenco ^[2] ; Peccinini, Rosangela Goncalves ^[1]

Afiliação do(s) autor(es)

^[1] Sao Paulo State Univ, Sch Pharmaceut Sci, Dept Nat Act Principles & Toxicol, Araraquara, SP - Brazil

^[2] Sao Paulo State Univ, Sch Pharmaceut Sci, Dept Clin Anal, Araraquara, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: BIOPHARMACEUTICS & DRUG DISPOSITION; v. 33, n. 9, p. 501-509, DEC 2012.
• Citações Web of Science: 2

Resumo

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 (C) 2012 John Wiley \& Sons, Ltd. (AU)

• Processo FAPESP: 08/57029-2 - Tratamento de tuberculose: estudo de interações farmacocinéticas da isoniazida
• Beneficiário: Elias Carvalho Padilha
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica