{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T17:28:19Z","timestamp":1760549299430,"version":"3.40.3"},"reference-count":17,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2012,10,25]],"date-time":"2012-10-25T00:00:00Z","timestamp":1351123200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biopharm &amp; Drug Disp"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>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\u2010effects 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 (<jats:italic>n<\/jats:italic>\u2009=\u200920) were divided into four groups and subjected to multiple oral doses for 7\u2009days according to the following treatments: water (group 1); 50\u2009mg\/kg INH (group 2); 50\u2009mg\/kg INH\u2009+\u2009100\u2009mg\/kg RMP (group 3) and 50\u2009mg\/kg INH\u2009+\u2009100\u2009mg\/kg RMP\u2009+\u200950\u2009mg\/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\u2009h 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 \u00a9 2012 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/bdd.1817","type":"journal-article","created":{"date-parts":[[2012,9,25]],"date-time":"2012-09-25T03:32:14Z","timestamp":1348543934000},"page":"501-509","source":"Crossref","is-referenced-by-count":2,"title":["Pharmacokinetic and safety evaluation of the use of ciprofloxacin on an isoniazid\u2010rifampicin regimen in rabbits"],"prefix":"10.1002","volume":"33","author":[{"given":"Elias Carvalho","family":"Padilha","sequence":"first","affiliation":[{"name":"Department of Natural Active Principles and Toxicology, School of Pharmaceutical Sciences S\u00e3o Paulo State University Araraquara SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rodrigo Vieira","family":"Pires","sequence":"additional","affiliation":[{"name":"Department of Natural Active Principles and Toxicology, School of Pharmaceutical Sciences S\u00e3o Paulo State University Araraquara SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco Antonio Ferraz Nogueira","family":"Filho","sequence":"additional","affiliation":[{"name":"Department of Natural Active Principles and Toxicology, School of Pharmaceutical Sciences S\u00e3o Paulo State University Araraquara SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diego Vinicius","family":"de Pontes Machado","sequence":"additional","affiliation":[{"name":"Department of Natural Active Principles and Toxicology, School of Pharmaceutical Sciences S\u00e3o Paulo State University Araraquara SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen Mariana","family":"Baldan","sequence":"additional","affiliation":[{"name":"Department of Natural Active Principles and Toxicology, School of Pharmaceutical Sciences S\u00e3o Paulo State University Araraquara SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcelo Gomes","family":"Davan\u00e7o","sequence":"additional","affiliation":[{"name":"Department of Natural Active Principles and Toxicology, School of Pharmaceutical Sciences S\u00e3o Paulo State University Araraquara SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel Leandro","family":"Campos","sequence":"additional","affiliation":[{"name":"Department of Natural Active Principles and Toxicology, School of Pharmaceutical Sciences S\u00e3o Paulo State University Araraquara SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iguatemy Louren\u00e7o","family":"Brunetti","sequence":"additional","affiliation":[{"name":"Department of Clinical Analysis, School of Pharmaceutical Sciences S\u00e3o Paulo State University Araraquara SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ros\u00e2ngela Gon\u00e7alves","family":"Peccinini","sequence":"additional","affiliation":[{"name":"Department of Natural Active Principles and 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