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BioMed Research International
Volume 2014, Article ID 570910, 5 pages
http://dx.doi.org/10.1155/2014/570910
Research Article

Effect of Experimentally Induced Hepatic and Renal Failure on the Pharmacokinetics of Topiramate in Rats

1Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait
2Department of Physiology and Pharmacology, School of Medicine, Al-Quds University, Abu Dees, West Bank, Jerusalem, Palestine

Received 23 August 2013; Revised 7 April 2014; Accepted 24 May 2014; Published 9 June 2014

Academic Editor: Manjari Tripathi

Copyright © 2014 Kamal M. Matar and Yasin I. Tayem. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

We aimed to investigate the effect of induced hepatic and renal failure on the pharmacokinetics of topiramate (TPM) in rats. Twenty-four Sprague-Dawley rats were used in this study. Renal or hepatic failure was induced by a single i.p. dose of 7.5 mg/kg cisplatin ( ) or 0.5 mL/kg carbon tetrachloride (CCl4) ( ), respectively. Three days after cisplatin dose or 24 h after CCl4 dose, the rats were administered a single oral dose of 20 mg/kg TPM. The plasma samples were quantified by LC-MS/MS method. Compared to control, plasma concentration-time profile in CCl4-treated and, to a lesser extent, in cisplatin-treated rats decreased more slowly particularly in the elimination phase. TPM oral clearance (CL/F) in CCl4-treated group was significantly lower than that in control ( ), whereas , T1/2, and Vd/F were significantly higher in CCl4-treated rats compared to the control ( ). The CL/F was not significantly different between cisplatin-treated rats and control ( ). However, in cisplatin-treated rats, the T1/2 and Vd/F were significantly higher than that in the control group ( ). Both conditions failed to cause a significant effect on or . The present findings suggest that induced hepatic or renal failure could modify the pharmacokinetic profile of TPM in the rat.