Sodium Valproate

Sodium Valproate

• CAS number 1069-66-5
• Formula C8H15NaO2
• Molecular Weight 166.19
• ATC code N03AG01
• Pub Chem 14047
• Chem Spider 13428

Chemical data

• Mol. mass 166.20 g/mol
• Pharmacokinetic data
• Bio-availability ?
• Protein binding 90-95%
• Metabolism 75% by CYP enzymes
• Half life 9-18 hours
• Excretion 20% excreted as glucuronide

Microbiological Test
Total plate count MAX 1000/g
Yeast&mold MAX 100/g
E.Coli Negative 

Description   
Sodium valproate is indicated mainly for complex or pure absence seizure, it can also be kinds to treat myoclonia or assist to treat it. Which is white powder, slightly subastringent, soluble to water.

Chemistry
Sodium valproate (INN) or valproate sodium (USAN) is the sodium salt of Valproic acid and is an anticonvulsantanticonvulsant used in the treatment of epilepsy and bipolar disorder, as well as other psychiatric conditions requiring the administration of a mood stabilizer. The intravenous formulations are used when oral administration is not possible.

• MF: C8H15NaO2
• MW: 166.20 g/mol
• Metabolism75% by CYP enzymes
• Half life9-18 hours
• Excretion: 20% excreted as glucuronide

Uses

• Sodium valproate is the widely used an anti-epileptic drug in the pediatric population. Nausea, vomiting, anorexia, amenorrhoea, sedation, tremor, weight gain, alopecia, and hepato-toxicity are the most common side effects of this drug.The hepatotoxicity may manifest in several ways: transient elevation of transaminase values, reversible hyperammonemia with liver disease, or Reye syndrome - like syndrome, or progressive hepatitis.
• Patients with epilepsy who are on sodium valproate have been reported to have low serum carnitine levels and this secondary carnitine deficiency has been reported in the literature. Prolonged treatment with sodium valproate more than other anticonvulsantsanticonvulsants, enhances renal losses of carnitine esters, lowers serum carnitine levels, and results in secondary carnitine deficiency.It also may cause a decrease in serum free carnitine levels by inhibition of plasmalemmal carnitine uptake.

Production

This compound has been obtained by two different ways:

• The reaction of dipropylcarbinoldipropylcarbinol with HBr gives 4-bromoheptane, which is treated with KCN to yield 2-propylpentanenitrilepropylpentanenitrile .Finally, this compound is hydrolyzed to the target compound with NaOH or with H2SO4.
• The condensation of cyanacetic acid ethyl ester with propyl bromide by means of sodium propoxide in propanol gives crude dipropylcyanaaceticdipropylcyanaacetic acid ethyl ester, which, without isolation, is hydrolyzed with NaOH in hot water yielding dipropylcyanaceticdipropylcyanacetic acid .The decarboxylationdecarboxylation of dipropylcyanaceticdipropylcyanacetic acid at 140-190°C affords the previously reported 2-propylpentanenitrilepropylpentanenitrile .

Safety Profile

All antiepilepic medications have been shown to be associated with higher risks of fetal abnormalities (mostly for spina bifida) since at least 1983 with the risks being related to the strength of medication used and use of more than one drug.Valproate has also been recognised as sometimes causing a specific facial changes ("facial phenotype") termed "fetal valproate syndrome".Sodium valproate has been associated with the rare condition paroxysmal tonic upgaze of childhood, also known as Ouvrier-Billson syndrome, from childhood or fetal exposure (this condition resolved after discontinuing valproate therapy)

Mechanism Of Toxic Effects

Valproate is a drug with anticonvulsant activity against a wide range of seizure types and appears to be well tolerated at therapeutic doses. In therapeutic use valproate's action may be related to altered turnover of GABA and actions on voltage sensitive sodium channels. The mechanisms involved in toxicity are unclear. It appears to have teratogenic effects in therapeutic doses.