doiSerbia

Current clinical evidence on topiramate pharmacokinetics

Jakovljević Mihajlo (Medicinski fakultet, Katedra za farmakologiju i toksikologiju, Kragujevac)
Jožef Maj (Farmaceutski fakultet, Katedra za biofarmaciju i farmakokinetiku, Ljubljana, Slovenija)
Vovk Tomaž (Farmaceutski fakultet, Katedra za biofarmaciju i farmakokinetiku, Ljubljana, Slovenija)
Janković Slobodan (Medicinski fakultet, Katedra za farmakologiju i toksikologiju, Kragujevac)
Grabnar Iztok (Farmaceutski fakultet, Katedra za biofarmaciju i farmakokinetiku, Ljubljana, Slovenija)

Topiramate is biochemically classified as a fructopyranose sulphamate. Discovered as early as 1979, during middle 1980's it was approved in many countries for the treatment of epilepsies and migraine prevention. More recently, in the experimental stage, possible new indications have been disclosed: treatment of obesity, bipolar disorder, also cessation of smoking, neuropathic pain, cerebral pseudotumour, bulimia, periventricular leucomalatia in preterm infants and alcohol addiction. Most epileptologists consider it to be the first choice antiepileptic drug in severe pharmacoresistant epilepsies. A substantial corpus of evidence in paediatric population has been accumulated that confirms its efficiency in the treatment of generalised tonic-clonic seizures, Lenox-Gestaut syndrome, partial, absence and combined seizures. Having a unique monosaccharide chemical structure among other anticonvulsant drugs, characterizes it with special pharmacokinetic features. This substance exhibits a low interindividual variability in plasma levels and hence it features predictable pharmacokinetics. A steady state plasma concentration of topiramate increases linearly with higher dosages. Serum protein binding is approximately 15%, and biologic half-life in healthy volunteers is considered to range from 20 to 30 hours. Mean expected distribution volume rates from 0.55-0.8 l/kg, and accordingly, the drug shows a low and saturable binding capacity toward erythrocytes. It has not been present at the market for a sufficiently long time that would enable us to speak about a significant accumulation of data on its metabolism based on post-registration 4th stage clinical trials. For this purpose, we have done a literature review in order to summarise so far reported experience on topiramate pharmacokinetics in patients and healthy adults. Deeper understanding of its pharmacokinetic profile could enable a better technological design of the produced drug and the choice of the adequate route of its administration, and accordingly a more rational treatment of severe epilepsies resistant to other drugs.

Keywords: topiramate, pharmacokinetics, plasma concentration, Epilepsy