Chemical formula: C₇H₁₁NO₂ Molecular mass: 141.168 g/mol PubChem compound: 3291
Ethosuximide is an anti-epileptic of the class of succinimides that apparently exerts multiple mechanisms of action. The activity of ethosuximide in absence type epilepsy seems to rely primarily on the inhibition of T-type calcium channels in the thalamus.
Ethosuximide is practically completely absorbed after oral administration. Cmax values of 18-24 μg/ml were measured after the intake of 1 g ethosuximide in three test persons after 1-4 hours.
In adults under long-term treatment at a dose of ca. 15 mg/kg body weight a plasma concentration of about 50 μg/ml was measured. At an oral dose of 1 mg/kg per day a plasma concentration of 2-3 μg/ml is to be expected.
Steady state is expected to occur 8-10 days after start of treatment. Despite significant interindividual variation of plasma concentrations at the same oral dose, dose-linear dependence of plasma concentration was established.
The therapeutic plasma concentration of ethosuximide is 40-100 μg/ml. Plasma concentrations of more than 150 μg/ml may have toxic effects.
Ethosuximide is not bound to plasma proteins.
Ethosuximide is present in liquor and saliva in the same concentration as in plasma. The apparent volume of distribution is specified to be approximately 0.7 l/kg body weight.
Ethosuximide is extensivly metabolised in the liver by oxidation. Several metabolites are produced, in particular the two diastereomeres of 2-(1-hydroxyethyl)-2-methyl succinimide and of 2-ethyl-2- methyl-3-hydroxysuccinimide. The metabolites are probably inactive.
Between 10% and 20% of ethosuximide only is excreted unchanged in the urine. The main metabolites of ethosuximide, the two diastereomeres of 2-(1-hydroxyethyl)-2-methyl succinimide and of 2-ethyl-2-methyl-3-hydroxysuccinimide are to some extent conjugated and excreted renally as glucuronide. After a single oral dose of 13.1-18.0 mg ethosuximide/kg body weight given to 12 male test persons (20-23 years, 57.2-114.8 kg body weight) plasma half-lives of 38.3-66.6 hours were measured.
After a single dose of 500 mg ethosuximide (capsules) given to 5 children, plasma half-lives of 25.7-35.9 hours were measured, with oral solution the plasma half-lives were 24.8-41.7 hours.
Ethosuximide passes into breast milk; the ratio of the ethosuximide concentration of breast milk vs. plasma is specified to be 0.94±0.06.
In a study in children (7-8.5 years, 12.9-24.4 kg body weight) Cmax values of 28.0-50.9 µg/ml were measured 3-7 hours after the children had taken a single dose of 500 mg ethosuximide.
Long-term treatment of children at 20 mg/kg body weight produces a plasma concentration of approximately 50 µg/ml. In children an oral daily dose of 1 mg/kg produces a plasma concentration of 1-2 µg/ml. Therefore, younger children require a slightly higher dose than older children.
Non-clinical data reveal no special hazard for humans based on conventional studies of acute and repeated dose toxicity
Ethosuximide did not reveal a potential for mutagenicity or chromosome aberrations when studied in vitro.
Long-term studies of the carcinogenetic potential in animals have not been performed. Embryotoxicity studies in rats and mice revealed a higher incidence rate of malformation and changes in behaviour.
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