I. Pharmaceutical characteristics
(1) Levamlodipine is a chiral drug in antihypertensive drugs.
Chiral drugs are used as a single enantiomer to reduce the dosage, reduce the risk of adverse events, and eliminate the burden of drug metabolism and elimination. 1992 the us food and drug administration requires that racemic drugs must be sold and applied as optically pure single enantiomers. The US Food and Drug Administration in China has made similar regulations.
Levamlodipine, the first chiral antihypertensive drug independently developed in China, was obtained by Shihuida Pharmaceutical Group (Jilin) Co., Ltd. through chiral resolution technology, and the pure levoisomer was obtained for the first time, and the invention patent and intellectual property rights of the compound were obtained. Levamlodipine besylate (Shihuida)? Name and list.
In 2003, the second-hand levoamlodipine drug was produced in Unacon by changing the acid radical method. Levamlodipine maleate (Xuanning)? , and obtain intellectual property rights. These two drugs are innovative drugs with patent rights and independent intellectual property rights developed by China's pharmaceutical industry.
(2) Pharmaceutical characteristics of L-amlodipine:
① Pharmacodynamic characteristics: The hypotensive effects of levoamlodipine besylate and levoamlodipine maleate are 65,438+0,000 times that of dextrorotators and 2 times that of racemates 65,438+0: 65,438+0. Dextroform has almost no antihypertensive effect, and sensitive patients may have symptoms such as headache, edema of limbs and facial flushing, but it is weaker than racemic amlodipine besylate.
② Pharmacokinetic characteristics: After taking racemic amlodipine, the half-life of levorotatory is significantly longer than that of dextrorotatory, the former is 50.6 hours and the latter is 35.5 hours. Left-handed absorption is better than right-handed absorption. The terminal elimination half-life is about 35 hours for healthy people, 50 hours for hypertensive patients, 65 hours for elderly patients and 60 hours for patients with impaired liver function, and renal insufficiency is not affected.
Second, pharmacological action and clinical evidence-based
(1) hypotensive effect: the right-handed levoamlodipine was removed by chiral drug resolution technology, effectively retaining the hypotensive effect of racemic amlodipine.
A randomized double-blind parallel study of levoamlodipine besylate and amlodipine besylate in the treatment of primary mild to moderate hypertension in China showed that levoamlodipine besylate 2.5 mg and amlodipine besylate 5 mg had similar antihypertensive effects, and the total effective rates of the two drugs were 84.9 1% and 77.45% respectively. At the same time, it was found that the blood pressure could still be kept below 140/90 mmHg after 24 hours and 48 hours of drug leakage, suggesting that the drug has a long-term antihypertensive effect.
Another study, "Levamlodipine maleate and amlodipine besylate in the treatment of mild to moderate essential hypertension", shows that both of them have the same long-term stable antihypertensive effect. Levamlodipine maleate is stable, long-term and safe, which can not only effectively control 24-hour blood pressure, but also inhibit early morning hypertension. Due to patent protection, the international research on the clinical application of L-amlodipine is mainly concentrated in Asian countries including South Korea and India.
Domestic research shows that the antihypertensive range and effective rate of levoamlodipine besylate are at least equivalent to other commonly used antihypertensive drugs. Levamlodipine besylate combined with antihypertensive drugs such as captopril, metoprolol, carvedilol or hydrochlorothiazide can further improve the antihypertensive effect.
Country? Eleventh five-year plan? The research results of the sub-project "Reversal effect of L-amlodipine on microalbuminuria in patients with poor blood pressure control" of the comprehensive prevention and treatment project of hypertension show that L-amlodipine combined with AT 1 receptor antagonist (sartan antihypertensive drugs) can significantly reduce microalbuminuria while reaching the standard of blood pressure; Studies on non-dipper elderly hypertensive patients suggest that taking L-amlodipine besylate during the day or at night can better correct high-load blood pressure at night, improve the rate of reaching the standard at night and control blood pressure variability.
Country? Twelfth Five-Year Plan? A large-sample, multi-center and prospective comparative study of levoamlodipine maleate and amlodipine besylate in the treatment of hypertension, a major scientific and technological project of new drug creation, aims to explore the antihypertensive drug treatment scheme suitable for China's national conditions. Studies have shown that levoamlodipine maleate has the same curative effect as imported amlodipine besylate, but it has different advantages in drug safety and pharmacoeconomics, and levoamlodipine maleate has fewer adverse reactions. Levamlodipine (2.5 ~ 5 mg, 1 time/day) is superior to lacidipine (4 ~ 8 mg, 1 time/day) in controlling blood pressure variability.
(2) Target organ protection: Levamlodipine (whether amlodipine besylate or amlodipine maleate) alone or in combination with other antihypertensive drugs can effectively lower blood pressure, reverse left ventricular hypertrophy, reduce proteinuria and protect renal function. The corresponding clinical observation was made in improving dynamic arteriosclerosis index and protecting vascular endothelial function, and the organ protection effect of L-amlodipine was determined.
Third, tolerance and security.
Levamlodipine effectively retains the pharmacological action of racemic amlodipine in lowering blood pressure, reduces the dosage by 50%, reduces the incidence of treatment-related adverse reactions, and makes it safer and more tolerant. Compared with racemic amlodipine, levoamlodipine has lower incidence of side effects such as edema and facial flushing, higher compliance and better tolerance. After amlodipine, nifedipine controlled/sustained-release tablets and felodipine sustained-release tablets were used in patients with edema, the incidence of adverse reactions of lower extremity edema decreased.
Fourth, clinical application
(1) indications: it is recommended to treat hypertension, especially hypertension in the elderly; Recommended for the treatment of hypertension and coronary heart disease angina pectoris; Recommended for hypertensive patients with target organ damage (left ventricular hypertrophy, microalbuminuria, carotid atherosclerosis and plaque, etc.). ). For patients with mild hypertension, L-amlodipine can be used as the first choice for monotherapy. For patients with refractory hypertension or other high-risk factors, one or more other antihypertensive drugs can be combined to ensure that blood pressure reaches the standard.
(2) Administration method: Generally, the initial oral dose is 2.5 mg 1 time, and the maximum dose is 5 mg 1 time. The initial dose of thin people, people with weak constitution, elderly patients or people with impaired liver function is 1.25 mg/day 1 time. If the blood pressure reaches the standard after 1 ~ 2 weeks or the symptoms of angina pectoris are not satisfied, the therapeutic dose can be gradually increased to the maximum dose. Renal insufficiency has no significant effect on the pharmacokinetic characteristics of this product and will not be eliminated by hemodialysis. Therefore, it can be used for patients with different degrees of renal insufficiency, and hemodialysis patients do not need to adjust the dose. The dose of elderly patients is the same as that of ordinary adults, but the treatment should start from a small dose, and if patients can tolerate it, it can be gradually increased to the therapeutic dose.
As a national innovative drug, L-amlodipine can lower blood pressure with high quality and protect target organs, and the price is more reasonable. Up to 20 16, 1 1, 86 academic papers on levoamlodipine have been published. Up to now, there are 23 domestic invention patents and 2 international invention patents1,which laid a foundation for the treatment of hypertension.