Edaravone is a kind of cerebral protective agent (free radical scavenger). Clinical study indicates that N£­acetylaspartate is a specific neuronal marker. In the early phase of cerebral infarction N-acetylaspartate (NAA) decreases radically. Edaravone was given to patients with acute cerebral infarction which can inhibit reduction of regional cerebral blood flow around infarction. 28 days later NAA in the edaravone treatment group is much higher than that of control group. Clinical study suggests that edaravone intravenously administered to rats after ischemia-reperfusion injury can prevent the development of cerebral edema and cerebral infarction attenuate neurogenic symptom and inhibit delayed neuronal death. Study suggests that edaravone can scavenge free radical inhibit lipid peroxidation and protect brain cell endothelial cells and neuron against oxidative stress.

Genetic toxicity: Edaravone Ames test CHL chromosome aberration test and mouse micronucleus test shows negative results.

Reproductive toxicity: In general reproductive toxicity test rats were administered with edaravone at a dosage of 3 mg/kg 20mg/kg and 200 mg/kg. Rats administered with edaravone at a dosage of 20 mg/kg and 200 mg/kg secrete brown urine shed tears and reduce independent activities with their mouth watering and weight and appetite loss. Average sexual cycle of female rats administered with edaravone at a dosage of 200 mg/kg prolongs. Reproductive capacity of female and male rats administered with edaravone at a dosage of 200mg/kg drops while residual ratio of fetal thymus rises. In a test conducted during the sensitive period to teratogenic agent pregnant rats were intravenously administered with edaravone at a dosage of 3 mg/kg 30 mg/kg and 300 mg/kg. Rats administered with edaravone at a dosage of 300mg/kg lost their appetite to a degree was prostrate and shed tears their gait being unstable spontaneous movement and weight growth speed decreasing. Weight of male rat fetus administered with edaravone and female rat fetus administered with 300 mg/kg edaravone is lower than that of control group. Visceral teratogenic rate of fetus in the edaravone treatment group rises with teratogenic auricle eyelid opening pendulous testicle and delayed vaginal opening. Pregnant New Zealand white rabbits were intravenously administered with edaravone at a dosage of 3mg/kg 20mg/kg and 100mg/kg. Pregnant New Zealand white rabbits intravenously administered with 100mg/kg edaravone secreted brown urine and shed tears with symptoms such as ataxic gait miosis respiratory disease and hind leg paralysis. Hyperaemia edema necrosis and inflammation occurred at injection position; Weight of placenta of white rabbits administered with edaravone at a dosage of 3mg/kg and 100mg/kg radically increases. In a toxicity test conducted during perinatal period pregnant Wistar rats were intravenously administered with edaravone at a dosage of 3 mg/kg 20mg/kg and 200mg/kg. Wistar rats administered with 200mg/kg edaravone lost their appetite to a degree with weight growth speed decreasing and symptoms such as head shaking eye blinking tears shedding and reduction of spontaneous movement. 20 days after neonatal rats were born open field test shows that movement times of neonatal rats administered with 20mg/kg and 200mg/kg rises.

According to foreign literature report:

Plasma drug concentration: Healthy adult male volunteers (five cases) and healthy senile volunteers above 65 years of age (five cases) were intravenously administered with edaravone at a dosage of 0.5mg/kg twice a day (thirty minutes once) for two days. Two days later parameters are calculated according to change in plasma drug concentration at the beginning of edaravone administration. Pharmacokinetics parameters: Healthy adult male volunteers (five cases) and healthy senile volunteers (five cases)

Cmax(ng/ml) 888¡À171 1041¡À106

t1/2¦Á(h) 0.27¡À0.11 0.17¡À0.03

t1/2¦Â(h) 2.27¡À0.80 1.84¡À0.17

Cmax(ng/ml) 888¡À171 1041¡À106

t1/2¦Á(h) 0.27¡À0.11 0.17¡À0.03

t1/2¦Â(h) 2.27¡À0.80 1.84¡À0.17

(Mean¡À standard deviation)

Plasma edaravone concentration in healthy adult male volunteers and healthy senile volunteers seems to disappear without accumulation.

Serum protein binding rate: In vitro test suggests that rate of binding of edaravone to human serum protein and to human serum albumin is 92% and 89% to 91% respectively.

Metabolism: According to results of study conducted for healthy adult male volunteers and healthy senile volunteers metabolites of edaravone in plasma include sulphate complex and glucuronic acid complex. Main metabolites of edaravone in urine include glucuronic acid complex and sulphate complex. Excretion: Healthy adult male volunteers and healthy senile volunteers were administered with edaravone injection at a dosage of 0.5mg/kg twice a day (thirty minutes once) for two days. Urine excreted 12 hours after the edaravone is given contains 0.7% to 0.9% of edaravone and 71.0% to 79.9% metabolites.

To relieve neurologic symptoms caused by acute cerebral infarction and enhance routine activity ability and alleviate functional disorders.

[Interactions]

1. When edaravone is used in combination with such antibiotics as cefazolin sodium piperacillin sodium and cefotetan there is a possibility of exacerbation of renal failure. Therefore when edaravone is used in combination with these antibiotics you have to detect and closely observe renal functions for many times.

2. Edaravone must be diluted with physiological saline on principle (When edaravone is diluted with liquid containing sugar concentration of edaravone will be reduced).

3. Edaravone should not be intravenously administered in combination with high-octane liquid and amino acid preparation or through the same channel (Combined administration would reduce edaravone concentration).

4. Do not use edaravone in combination with antiepileptic drugs such as diazepam and phenytoin sodium (turbidity would occur).

5. Do not use edaravone in combination with canrenoate potassium (turbidity would occur).

According to observation of 569 patients in Japan adverse reactions were found in 26 patients (4.57). Main adverse reactions include abnormal liver functions found in 16 patients (2.81%) and tetter found in 4 patients (0.70%). Abnormal change in clinical detection results were found in 122 patients (21.4%). AST (aspartate aminotransferase) rise was found in 43 in 558 patients (7.71%) and ALT (alanine aminotransferase) rise was found in 46 in 559 patients (8.23%).
Severe adverse reactions include:

1. Acute renal failure (degree of renal failure is unknown). you have to detect and observe renal functions for many times during the administration of edaravone; cease giving edaravone to patients and handle the situation immediately after decline in renal functions or oliguria is found.

2. Abnormal liver functions and icterus accompanied with rise in AST ALT ALP ¦Ã-GT and LDH (degree of abnormal liver functions and icterus is still unknown). You have to detect and closely observe liver functions during the administration of edaravone. Cease giving earavone to patients and handle the situation immediately after abnormal liver functions and icterus are found.

3. Thrombocytopenia (degree is unknown). There is symptom of thrombocytopenia. You have to closely observe during the administration of edaravone. Cease giving edaravone and handle the situ