Epitomax is an antiepileptic drug, belongs to the class of sulfate-substituted monosaccharides. It blocks sodium channels and suppresses the occurrence of repetitive action potentials against the background of prolonged depolarization of the neuron membrane. Epitomax increases the activity of gamma-aminobutyric acid (GABA) against several subtypes of GABA receptors (including GABA receptors), as well as modulates the activity of GABA receptors themselves, prevents activation of kainate/AMPK (a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid)-receptors to glutamate, does not affect N-methyl-D-aspartate (NMDA) activity against the NMDA-receptor subtype. These effects of Epitomax are dose-dependent at plasma concentrations of Epitomax of 1 to 200 μmol/L, with minimal activity between 1 and 10 μmol/L.
In addition, epitomax inhibits the activity of some carboanhydrase isoenzymes (II-IV). Epitomax is significantly inferior to acetazolamide, a known carboanhydrase inhibitor, in terms of the severity of this pharmacological effect, so this effect of Epitomax is not a major component of its antiepileptic activity. After oral administration Epitomax is quickly and well absorbed from the gastrointestinal tract. Bioavailability is approximately 81%. After oral administration of 400 mg Epitomax, Cmax of 1.5 µg/ml is reached within 2 h. Food intake has no clinically significant effect on the bioavailability of Epitomax. Cmax after multiple oral doses of 100 mg of Epitomax twice a day averaged 6.76 mcg/ml.
The pharmacokinetics of Epitomax is linear, plasma clearance remains constant, and the area under the “concentration-time curve” (AUC) in the dose range from 100 to 400 mg increases in proportion to the dose. The plasma protein binding for Epitomax is 13-17% in the plasma concentration range of 0.5-250.0 µg/ml. After a single dose of up to 1200 mg, the average Vd is 0.55-0.8 L/kg. The Vd value depends on gender: in women it is about 50% of the values observed in men, which is associated with a higher content of adipose tissue in women.
Cssmax when taking Epitomax in patients with normal renal function is reached in 4-8 days. It penetrates into breast milk and through the placental barrier. After oral administration, about 20% of the administered dose is metabolized. It is metabolized by hydroxylation, hydrolysis and glucuronidation. However, in patients receiving concomitant therapy with antiepileptic drugs, which are inducers of microsomal enzymes, the metabolism of Epitomax was increased up to 50%. Six virtually inactive metabolites were isolated and identified from blood plasma, urine, and feces. When concomitant administration of cytochrome P450 isoenzyme inducers, the metabolism of epitomax was up to 50%.
The main route of excretion of unchanged topiramate (about 70%) and its metabolites is the kidneys. After oral administration, the plasma clearance of topiramate was 20-30 ml/min. After multiple oral doses of 50 and 100 mg twice daily, the plasma elimination half-life (T1/2) of topiramate averages 21 hours. It is eliminated from plasma by hemodialysis.
Pharmacokinetics in special clinical cases. Renal and plasma clearance of Epitomax in mild renal failure (creatinine clearance more than 70 ml/min) is not changed. In moderate renal failure (creatinine clearance 30-69 ml/min) renal and plasma clearance of epitomax is decreased by 42%, and in severe renal failure (creatinine clearance less than 30 ml/min) renal and plasma clearance of epitomax is reduced by 54% or more.