Effect of Experimentally Induced Hepatic and Renal Failure on the Pharmacokinetics of Topiramate in Rats. (9th June 2014) - Matar, Kamal M.
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 (n = 8 ) or 0.5 mL/kg carbon tetrachloride (CCl4 ) (n = 8 ), 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 (P < 0.001 ), whereas AUC 0 − ∞, T1/2, and Vd/F were significantly higher in CCl4 -treated rats compared to the control (P < 0.01 ). The CL/F was not significantly different between cisplatin-treated rats and control (P > 0.05 ). However, in cisplatin-treated rats, the T1/2 and Vd/F were significantly higher than that in the control group (P < 0.01 ). Both conditions failed to cause a significant effect on C max or T max . The present findings suggest that induced hepatic or renal failure could modify the pharmacokinetic profile of TPM in the rat.