Wanquan Lee Tae Commodity Introduction
Wanquan Lee Tae
Generic name: riluzole tablets
Manufacturer: Wante Pharmaceutical (Hainan) Co., Ltd.
Approval number: National Medicine Zhunzi H20073 149
Drug specification: 50mg*24 tablets.
Wanquan Lee Tae Manual
Trade name Wan Tai
Li Ming general Lu Zuo pian
English name Riluzole tablets
Left piece of Chinese phonetic alphabet
The main ingredient is Wanquan, and the main ingredient is riluzole.
The chemical name is pk-26 124, Rp-54274, and the chemical name is 2- chloro -6- trifluoromethylbenzothiazole.
Characteristic Riluzole tablets are white or white-like tablets.
Indications are all suitable for the treatment of amyotrophic lateral sclerosis, prolonging life or mechanical ventilation time. But it is not suitable for other forms of motor neuron diseases.
Administration and dosage: Adults take 1 tablet twice a day; Not recommended for children.
Adverse reactions Common adverse reactions include fatigue, nausea, headache, abdominal pain, vomiting, increased liver function index, dizziness, tachycardia, drowsiness and confusion around the mouth.
In the experiments of rats and rabbits, riluzole tablets have embryotoxicity, which reduces the chances of conception and increases the fetal mortality. It is not recommended for pregnant women. The drug is secreted in the milk of lactating rats, so ALS patients should not breastfeed when using riluzole tablets.
Riluzole tablets can increase transaminase, especially Zat, which can reach 2-5 times of the normal upper limit, so liver function should be checked before use and monitored after medication. If ALT exceeds the normal value 10 times or jaundice occurs, the drug should be stopped immediately. After 2 months of drug withdrawal, ALT can return to normal value.
The common adverse reactions of riluzole tablets are fatigue 17.5%, nausea 4.2%, headache 6.8%, abdominal pain 5. 1%, pain 4.8%, vomiting 3.8%, dizziness 3.3%, heart rate increase 3.0%, drowsiness 2.0%, and abnormal sensation around the mouth/. Rare adverse reactions include fever and agranulocytosis, which usually appear after 2 months. It is recommended that patients have blood tests when they have a fever.
2 16 trial and 30 1 trial ALSo evaluated the safety of riluzole tablets in patients with als. Compared with the placebo group, the adverse reactions such as fatigue, nausea, ALT elevation and anorexia were more common in the treatment group. The incidence of termination of treatment due to adverse reactions was 14% in the riluzole tablet group and 1 1% in the placebo group.
The incidence of serum alanine aminotransferase (ALT) increased in patients who used riluzole tablets. The number of patients who stopped cleaning treatment because of the increase of ALT was 3%. The elevated ALT level rarely exceeds 5 times the upper limit of the normal range (LUN), and the elevation of ALT below this level is reversible. Even if we continue to use riluzole tablets, the ALT level will drop to less than 2 times of LUN within 2-6 months.
Although riluzole tablets act on sodium channels, it has no effect on the vascular system, blood pressure and heart rate of patients. This is because riluzole tablets specifically stabilize the inactive state of sodium channels and have a strong effect on high-frequency depolarization cells, while myocardial cells have low depolarization frequency and negative resting membrane potential, which may be insensitive to riluzole tablets.
In addition, only a small amount of riluzole tablets are exposed to myocardium in vivo, which also makes the drug have little effect on the heart. In the global large-scale pre-medication plan of riluzole tablets, the adverse reactions of patients in American group 160O were similar to those in the above two experiments.
Matters needing attention
(1) Start treatment under the guidance of experts;
(2) It is forbidden for patients with severe liver disease, pregnant women and lactating women, and should be used with caution for those with renal insufficiency;
(3) Patients with mild and moderate liver diseases should monitor the serum transaminase before and during treatment, and stop treatment if the transaminase rises to 5 times the normal value;
(4) Remind patients to report febrile diseases caused by slight neutropenia.
Pregnant women and lactating women are forbidden to take drugs.
At present, there is no research data on children taking riluzole tablets.
The medication for elderly patients is the same as that for healthy adults.
Cytochrome p450 1A2 is the main metabolic enzyme, and CYp 1A2 inhibitors (phenacetin, theophylline, amitriptyline and quinolones) may reduce the clearance rate of the drug. CYp 1A2 inducers (smoking, rifampicin, omeprazole) may increase the clearance rate of the drug.
Drug overdose has no effective antidote or treatment for riluzole overdose. When riluzole overdose occurs, we should immediately stop the treatment of riluzole, support the treatment and directly relieve the symptoms. Methemoglobinemia occurs when the dose is too high, which can be quickly recovered after treatment with methylene blue.
pharmacological action
1. Amyotrophic lateral sclerosis (ALS) or motor neuron disease is a progressive fatal disease. There are two forms of this disease: limb disease or medullary disease. Both of them are characterized by the loss of upper and lower motor neurons, which leads to progressive irreversible muscle wasting and weakness. Although the pathogenesis of the disease is not fully understood, glutamate toxicity is a possible cause of neuronal damage. Therefore, drugs that can regulate the level of glutamate in the central nervous system have been regarded as a feasible treatment.
Riluzole, a benzothiazole drug, is such an anti-glutamate drug, and its neuroprotective mechanism is complex, involving several different processes. It is known that it can inhibit the release of presynaptic glutamate, and bind to the receptor to prevent the activation of glutamate. Wanquan can also inactivate potential-dependent sodium channels in nerve endings and cell bodies and stimulate G protein-dependent signal transduction.
In vitro, it can protect cultured motor neurons from the toxic effect of glutamate activation and prevent ALS patients from neuron death caused by hypoxia or exposure to toxic factors in cerebrospinal fluid. In the mouse model of spinal motor neuron degeneration, omnipotent can improve its activity.
2. In the cell culture model in vitro, riluzole tablets can obviously prevent acute and chronic cell damage caused by glutamic acid, suggesting its cytoprotective effect. In the animal model of familial amyotrophic lateral sclerosis (FALS), riluzole tablets can prolong the survival time and/or improve the activity of FALS-SOD transgenic mice.
1994 Bensimon et al. 2 reported for the first time a prospective, randomized, double-blind and placebo-controlled trial of riluzole tablets, which treated 55 cases of MS/kloc-0. Results After 1 year, the survival rate of patients increased significantly, which proved that the curative effect of riluzole tablets on patients with ball symptoms was more obvious than that of patients with limb symptoms. The decline of muscle strength in the treatment group was significantly slower than that in the control group.
Subsequently, Lacomblez and others reported the treatment results of 959 cases of multi-center ALS, and thought that 100 and 200mg? The risk of tracheotomy or death in treatment group D was reduced, and there was no significant difference. Patients with limb attack and ball attack are equally effective. The exact neuroprotective mechanism of riluzole tablets is not completely clear. Dobl believes that there are four main mechanisms:
① Blocking glutamate receptors directly but non-competitively;
② Inhibition of presynaptic glutamate release;
③ Turn off the voltage-dependent sodium channel;
④ Stimulate 0 protein coupled signal transduction system. According to the past clinical experience, it is considered that riluzole tablets can delay the time before tracheotomy in ALS patients and delay the deterioration of myasthenia gravis, but it cannot reverse the course of disease.
The cause of 3.3. ALS is still unknown. Except for 5%- 10% patients with family history, most of them are sporadic. At present, there are many hypotheses about the etiology of ALS, among which glutamate excitotoxicity and oxidative overreaction are the focus of current research.
Glutamate is the main excitatory neurotransmitter in mammalian brain. About one-third of the fast excitatory synapses in the central nervous system are formed by glutamate-mediated axons in some glutamatergic neurons and motor neurons.
Under physiological conditions, glutamic acid is released into the synaptic space under the action of excitatory impulses, spreads to the postsynaptic membrane, and reacts with NMDA(N- methyl -D? F- aspartic acid receptor and AMpA receptor stand together, which leads to the opening of receptor-dependent ion channels and the inflow of sodium ions and calcium ions, thus improving the excitability of motor neurons. The remaining glutamic acid is absorbed by presynaptic membrane receptor or decomposed by peripheral glial cells.
However, when the excessive release or clearance pathway of glutamic acid I is abnormal, too much glutamic acid accumulates in the synaptic cleft and acts on the corresponding receptors excessively and persistently. It leads to excessive influx of sodium ions, which in turn leads to osmotic edema and rupture of cells. The influx of calcium ions and extracellular secretion mediated by endogenous calcium ions further activate various protein kinases and produce a large number of free radicals, which leads to attacks on their own structures. This destructive effect is called excitatory amino acid neurotoxicity.
Riluzole tablets can at least block the above links from the following three aspects:
Experiments show that riluzole tablets can reduce the release of glutamic acid, but its mechanism needs further study.
B riluzole tablets can block excitatory amino acid receptors, which is a non-competitive inhibition and reversible.
C riluzole tablets can also directly inhibit the voltage saddle sodium channels on nerve endings and neuronal cell bodies, thus inhibiting the excitability of presynaptic membrane and partially preventing the excitability of postsynaptic membrane receptor coupling. Therefore, riluda can directly or indirectly reduce the excitatory neurotoxicity of glutamic acid through various ways, which is the pharmacological basis of riluzole tablets in the treatment of ALS.
pharmacokinetics
Wanquan can be absorbed quickly after oral administration, reaching the peak of blood concentration within 60-90 minutes. About 90% of the drug was absorbed, and the absolute bioavailability was 60%. Wanquan is metabolized by the liver and excreted mainly by urine, and its elimination half-life is 9- 15h. The oral absorption rate is about 90%, which is easy to pass through the blood-brain barrier. After oral administration, the peak plasma concentration reached 65438 0.0-65438 0.5h. The peak concentration and dose (25? 100mg, q 12h) showed a linear correlation. High-fat diet can reduce the peak concentration and area under the curve.
90% drugs bind to plasma proteins, mainly albumin and lipoprotein. The repeated dose of 1 week can reach the steady-state plasma concentration. The main metabolic pathways are the catalysis and glucuronidation of mitochondrial P isoenzyme CYp 1A2, and only 2% of riluzole tablets are discharged in the original form.
In healthy male volunteers, the pharmacokinetics of riluzole was evaluated by a single oral dose of 25 to 300mg and a repeated oral dose of 25 to 100mg twice a day. There is a linear relationship between the increase of blood drug concentration level and dose. Its pharmacokinetics has nothing to do with dose.
When repeated doses (50 mg of riluzole tablets, twice a day, for 10 days) were given, the accumulated amount of riluzole prototype in plasma was twice that of single dose, and reached a steady state within 5 days. Riluzole is absorbed rapidly after oral administration, reaching a large plasma concentration within 60 ~ 90 minutes (Cmax= 173? 72 (standard deviation) ng/ml). About 90% of the dose was absorbed and the absolute bioavailability was 60? 18%。 .
The prepared human liver was used to show that cytochrome p450 1A2 was the main isoenzyme related to the in vitro metabolism of riluzole. The metabolites in urine are 3 kinds of phenol derivatives, 1 urea derivatives and protoriluzole. The identified and unbound metabolites do not show the pharmacodynamic characteristics of riluzole in animals, so they have not been studied in humans. Excretion and excretion half-life are 9 to 15 hours. Riluzole is excreted mainly through urine.
The total urinary excretion rate is 90% of the dose. Glucuronic acid derivatives account for more than 85% of metabolites in urine. Only 2% dose of riluzole exists in urine in its original form. The pharmacokinetic parameters of riluzole in elderly healthy volunteers have not changed, so there is no special requirement for the use of riluzole in the elderly population.
There is no significant difference in the metabolism of this product between patients with renal insufficiency and healthy adults, but the AUC of patients with mild and moderate chronic hepatic insufficiency increased by 65438 0.7 times and 3 times respectively, suggesting that patients with liver disease and patients with transaminase higher than 3 times the upper limit of normal value should not use riluzole.
Specifications 50mg*24 tablets
Store in a cool and dry place.
Valid for two years.
The approval number is National Medicine Zhunzi H20073 149.
Manufacturer Wante Pharmaceutical (Hainan) Co., Ltd.
Efficacy and role of Wanquanlitai Wanquanlitai is suitable for the treatment of amyotrophic lateral sclerosis, prolonging life or mechanical ventilation time. But it is not suitable for other forms of motor neuron diseases.
Frequently asked questions about taking Wanquanlitai
Q: Wanquanlitai is a new drug for treating motor neuron diseases, and it is the only drug that can delay the progress of amyotrophic lateral sclerosis. Wanquanlitai can penetrate the blood-brain barrier, inhibit the activity of excitatory amino acids, stabilize the inactivation of voltage-dependent sodium channels, and produce neuroprotective effects. Although Wanquanlitai is effective, many patients are often more concerned about its side effects when using Wanquanlitai. So, does Wanquanli have too many side effects?
A: The common side effects of Wanquanli are fatigue, nausea, headache, abdominal pain, vomiting, increased liver function, dizziness, tachycardia, drowsiness and confusion around the mouth. In the experiments of rats and rabbits, riluzole tablets have embryotoxicity, which reduces the chances of conception and increases the fetal mortality. It is not recommended for pregnant women. The drug is secreted in the milk of lactating rats, so ALS patients should not breastfeed when using riluzole tablets. 2 16 trial and 30 1 trial ALSo evaluated the safety of riluzole tablets in patients with als. Compared with the placebo group, the adverse reactions such as fatigue, nausea, ALT elevation and anorexia were more common in the treatment group. The incidence of termination of treatment due to adverse reactions was 14% in the riluzole tablet group and 1 1% in the placebo group.