Edaravone Injection

Edaravone Injection

Generic name: Edaravone Injection
Brand name: Bicun
Composition: 3-methyl-1-phenyl-2-pyrazolin-5-one
Chemical structure:


 

Molecular formula: C10H10N2O
Molecular weight: 174.20
Strength:(1)5ml:10mg (2)20ml:30mg
Discription:
This product is a kind of transparent liquid from colorless to pale yellow (or yellowish green)
Indications:Used to improve the neurologic symptoms, daily living ability and dysfunction caused by acute
cerebral infarction.
Dosage and Administration:
30mg/dose, twice a day. Intravenous drip finished within 30 minutes after diluted with normal saline. The
treatment course is within 14 days, and it is suggested that the drug is given within 24 hours as far as possible
after the onset of the disease.
Precaution:
1.Patients with mild and moderate renal impairment must take it carefully, since it may aggravate renal failure.
2. Patients with liver function damage must be careful because of its possibility to aggravate the damage of
liver function.
3. Patients with heart disease must be careful because of its possibility to aggravate the heart disease, or to
cause renal insufficiency.
4. Elderly patients must be careful (there have been several death case reports)
As there are cases of exacerbation of acute renal insufficiency or deaths caused by renal failure, several
renal function detections should be conducted during the product delivery process. Furthermore, it should
also be observed after finishing the delivery process. If there are symptoms of renal function decrease or
oliguria, immediately stop the drug and conduct appropriate processing. Besides, special attention should be
paid among elderly patient as there are many death case reports (most of them are above 80 years old).
Pharmacology and toxicology:
Pharmacological action
Edaravone is a kind of brain protective agent (free radical scavenger). Clinical research suggests that N-
acetyl aspartate (NAA) is a marker of specific survival nerve cells, and it decreases sharply  at the beginning
of the onset of cerebral infarction. Used in patients with acute cerebral infarction, edaravone can inhibit the
decrease of regional cerebral blood flow around the infarction, so that the NAA content in the brain is
significantly higher than that in glycerol control group on the twenty-eighth day after onset. Preclinical studies
suggest that edaravone which is administered intravenously in rats after ischemia / reperfusion, can prevent
development of cerebral edema and cerebral infarction, alleviate the accompanying neurological symptoms
and inhibit delayed neuronal death. Mechanism research suggesst that edaravone can scavenge free radicals
and inhibit lipid peroxidation, thereby inhibiting oxidative damage of brain cells, vascular endothelial cells and
neurons.

Toxicology research
Genotoxicity: Results in edaravone's Ames test, CHL chromosome aberration test and micronucleus test in
mice were all negative.
Reproductive toxicity: in general reproductive toxicity test in which rats were treated with edaravone 3, 20,
200mg/KG, animals in 20, 200mg/Kg groups had orange-brown urine color, lacrimation, salivation and
decreased locomotor activity, body weight and food intake, while in the 200mg/Kg group the average sexual
cycle of female rats extended, the fertility of female and male rats was reduced and the fetal thymus residual
rate increased. In toxicity test during the teratogenic sensitive period, intravenous injections of edaravone 3,
30, 300mg/Kg were conducted to pregnant rats. In the 300mg/Kg group the female rat's food intake
decreased and their body weight increase slowed down. Male fetus weight in all groups and that of the female
ones in 30mg/Kg group were lower than those of the control group. In all groups fetal visceral malformation
rate increased and there was a delay tendency in auricle expansion, palpebral dehiscence, testicular drooping
and vaginal opening.
Pharmacokinetics:
According to foreign literature:
Blood concentration
Healthy adult male subjects (5 cases) and healthy elderly subjects over 65 years old (5 cases), with0.5 mg/Kg
dose, twice a day, intravenous infusion within 30 minutes each time. After 2 days of medication, the drug
concentration changes in plasma and parameters obained from the begining of the administration are shown
in the following figures:


In both healthy adult male subjects and healthy elderly subjects, the drug concentration in the plasma was
almost equally disappearing, and no accumulation was found.
Serum protein binding rate  Vitro test results showed that the binding rates of human serum protein and
human serum albumin in edaravone were 92% and 89 to 91%, respectively.
Metabolism  The metabolites of edaravone in plasma are the complex of sulphuric acid and the complex of
glucuronic acid. The main metabolites in urine are glucuronic acid complex and sulphuric acid complex.
 Excretion  Healthy adult male subjects and healthy elderly subjects received this product twice a day with
0.5 mg/Kg each time, intravenous drip whithin 30 minutes, for 2 consecutive days. The excretion of urine
contained by the 12th hour after administration 0.7% to 0.9% raw drugs and 71% to 79.9% metabolites.
Storage:
Protect from light and keep in the shade (no more than 20ºC)
Packs:
(1) Medium borosilicate glass ampoule, 5ml/ampoule, 6 ampoules per box.
(2) Medium borosilicate glass ampoule, 20ml/ampoule, 6 ampoules per box; 4 ampoules per box.
Shelf-life:24 months