title: 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 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.
authors.affiliation: Department of Natural Active Principles and Toxicology, School of Pharmaceutical Sciences, São Paulo State University, Araraquara, SP, Brazil.
authors.forename: Elias Carvalho
authors.initials: EC
authors.lastname: Padilha
authors.forename: Rodrigo Vieira
authors.initials: RV
authors.lastname: Pires
authors.forename: Marco Antonio Ferraz Nogueira
authors.initials: MA
authors.lastname: Filho
authors.forename: Diego Vinicius
authors.initials: DV
authors.lastname: de Pontes Machado
authors.forename: Helen Mariana
authors.initials: HM
authors.lastname: Baldan
authors.forename: Marcelo Gomes
authors.initials: MG
authors.lastname: Davanço
authors.forename: Michel Leandro
authors.initials: ML
authors.lastname: Campos
authors.forename: Iguatemy Lourenço
authors.initials: IL
authors.lastname: Brunetti
authors.forename: Rosângela Gonçalves
authors.initials: RG
authors.lastname: Peccinini
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D002939:Ciprofloxacin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004338:Drug Combinations; D007538:Isoniazid / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D008297:Male; D011817:Rabbits; D012293:Rifampin / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D000904:Antibiotics, Antitubercular; D004338:Drug Combinations; D002939:Ciprofloxacin; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D001663:Bilirubin; D007538:Isoniazid; D012293:Rifampin