topiramate and Kidney-Diseases

Topiramate, a sulfamate-substituted monosaccharide, is a new antiepileptic drug (AED) approved as adjunctive therapy for partial-onset seizures in adults. Topiramate is rapidly absorbed, has linear pharmacokinetics, minimal protein binding and a long half-life facilitating a twice-daily dosage regimen. Topiramate has little effect on the plasma concentrations of other AEDs with the exception of phenytoin, concentrations of which may increase in some patients when topiramate is added to the therapy. Topiramate metabolism is increased when administered with carbamazepine or phenytoin. In the absence of enzyme-inducing AEDs, topiramate is eliminated primarily by renal excretion, with 50 to 80% of a dose excreted as unchanged topiramate. In 6 double-blind, placebo-controlled trials, topiramate was shown to be well tolerated and effective as adjunctive therapy for partial-onset seizures in adults. Topiramate consistently reduced seizures across all patient groups defined by age, gender and baseline seizure frequency. Adverse effects were generally mild-to-moderate CNS-related effects and often resolved spontaneously or with slowing of topiramate titration and/or reduction of the dosage of concomitant AEDs. Clinical studies are currently evaluating the effectiveness and safety of topiramate as monotherapy and adjunctive therapy in children with partial seizures, in patients with Lennox-Gastaut syndrome and in patients with generalised tonic-clonic seizures of non-focal onset. Preliminary findings suggest that topiramate has a broad spectrum of clinical use.

Topics: Adult; Aged; Anticonvulsants; Child; Drug Interactions; Epilepsy; Fructose; Humans; Kidney Diseases; Liver Diseases; Topiramate

Previous studies have shown that generation of free radicals is increased following pentylenetetrazol kindling, due to increased cytosolic Ca2+ concentrations. Topiramate, a voltage-gated calcium channel inhibitor, has an evident effect in the treatment of childhood epilepsy; however, topiramate may cause nephrotoxicity. We investigated the effects of topiramate and vitamin E administration on pentylenetetrazol-induced nephrotoxicity in rats by evaluation of lipid peroxidation, nitric oxide, glutathione peroxidase, catalase and superoxide dismutase values. Forty male Wistar rats were randomly divided into five equal groups. Group 1 was used as control and group II received a single dose of pentylenetetrazol. Fifty and 100 mg/kg topiramate daily were intragastrically administered to rats in groups III and IV for 7 days, respectively. Intragastric 100 mg topiramate (daily for 7 days) and intraperitoneal vitamin E (150 mg/kg, daily for 3 days) combination were given to animals in group V before a single-dose pentylenetetrazol administration. Serum and kidney samples were taken after 3 hr of pentylenetetrazol administration. Pentylenetetrazol resulted in a significant increase in nitric oxide levels of serum and kidney, and lipid peroxidation levels of kidney although superoxide dismutase and catalase activities in the kidney was reduced by pentylenetetrazol administration. The lipid peroxidation levels in serum and kidneys and the nitric oxide levels in kidneys of groups III, IV and V were decreased by topiramate although the superoxide dismutase and catalase activities in the kidneys were increased. Lipid peroxidation and nitric oxide levels were reduced by the topiramate and vitamin E combination compared to only topiramate. Glutathione peroxidase activity was not affect by pentylenetetrazol, topiramate and vitamin E administrations. In conclusion, topiramate and vitamin E have protective effects on pentylenetetrazol-induced nephrotoxicity by inhibition of free radicals and by support of the antioxidant redox system.

Topics: Animals; Anticonvulsants; Antioxidants; Catalase; Dose-Response Relationship, Drug; Drug Therapy, Combination; Epilepsy; Fructose; Glutathione Peroxidase; Kidney; Kidney Diseases; Lipid Peroxidation; Male; Nitric Oxide; Pentylenetetrazole; Rats; Rats, Wistar; Superoxide Dismutase; Topiramate; Vitamin E