title: Effect of experimentally induced hepatic and renal failure on the pharmacokinetics of topiramate in rats.
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 AUC0-∞, 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 Cmax or Tmax. The present findings suggest that induced hepatic or renal failure could modify the pharmacokinetic profile of TPM in the rat.
authors.affiliation: Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait.
authors.forename: Kamal M
authors.initials: KM
authors.lastname: Matar
authors.affiliation: Department of Physiology and Pharmacology, School of Medicine, Al-Quds University, Abu Dees, West Bank, Jerusalem, Palestine.
authors.forename: Yasin I
authors.initials: YI
authors.lastname: Tayem
mesh_terms: D000818:Animals; D019440:Anti-Obesity Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology; D002251:Carbon Tetrachloride / Q000633:toxicity; D002252:Carbon Tetrachloride Poisoning / Q000378:metabolism / Q000473:pathology; D002945:Cisplatin / Q000009:adverse effects / Q000494:pharmacology; D004195:Disease Models, Animal; D005632:Fructose / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D017093:Liver Failure / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D051437:Renal Insufficiency / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D000077236:Topiramate
chemical_list: D019440:Anti-Obesity Agents; D000970:Antineoplastic Agents; D000077236:Topiramate; D005632:Fructose; D002251:Carbon Tetrachloride; D002945:Cisplatin