What Is Lercanidipine?

Chinese name: Le card dipine

This product is a third-generation dihydropyridine calcium channel blocker. Its mechanism of action is similar to that of similar drugs, which can reversely block Ca2 + influx of vascular smooth muscle cell membrane L-type calcium channels, expand peripheral blood vessels and reduce blood pressure.

Basic information of Lecardipine

Chinese name: Le card dipine

Chinese alias: 1,4-dihydro-2,6-dimethyl-4- (3-nitrophenyl) -3,5-pyridinedicarboxylic acid 2-[(3,3-diphenylpropyl) Methylamino] -1,1-dimethylethyl methyl ester

English name: Lercanidipine

English alias: (±) -2-((3,3-diphenylpropyl) (methyl) amino) -1,1-dimethylethyl methyl 2,6-dimethyl-4- (3-nitrophenyl) -1,4-dihydropyridine-3 , 5-dicarboxylate; 1,4-Dihydro-2,6-dimethyl-4- (3-nitrophenyl) -3,5-pyridinedicarboxylic Acid 2-[(3,3-Diphenylpropyl) methylamino] -1,1-dimethylethyl Methyl Ester; 3,5-pyridinedicarboxylic acid, 1,4-dihydro-2,6-dimethyl-4- (3-nitrophenyl)-, 2-[(3,3-diphenylpropyl) methylamino] -1,1-dimethylethyl methyl ester ; Masnidipine; Methyl 1,1-Dimethyl-2- [N- (3,3-diphenylpropyl) -N-methylamino] ethyl 2,6-Dimethyl-4- (3-nitrophenyl) -1,4-dihydropyridine-3, 5-dicarboxylate; 1-[(3,3-diphenylpropyl) (methyl) amino] -2-methylpropan-2-yl methyl 2,6-dimethyl-4- (3-nitrophenyl) -1,4-dihydropyridine-3, 5-dicarboxylate

CAS: 100427-26-7

Molecular formula: C36H41N3O6 ^[1]

Molecular weight: 611.7272

[] Lecardipine [Chemical Structural Formula]

1,4-dihydro-2,6-dimethyl-4- (3-nitrophenyl) -3,5-pyridinedicarboxylic acid 2-[(3,3-diphenylpropyl) methylamino- 1,1-dimethylethyl methyl ester

[Appearance] White or light yellow solid

[Molecular formula] C15H19N3O5S

[Molecular weight] 611.73.

[CAS No.] 100427-26-7

[Quality Standard] Content> 99%

Melting point: 118-120 ° C

[Function and use] Pharmaceutical intermediate

Lercanidipine drug name

Lercanidipine

Drug aliases: Zainin Lerdip, Zanidip, Masnidipine

Lercanidipine formula

(±) -2-[(3,3) -diphenylpropyl] methylamino-1,1-dimethylethyl 1,4-dihydroxy-2,6-dimethyl-4- (m-nitro Phenyl 0-3,5-dihydroxy acid pyridine hydrochloride.

Lecardipine formulation specifications

Film-coated tablets 10 mg

Lercanidipine pharmacology and toxicology

This product has a high lipophilicity, so its onset time is slow and its duration is long. In vitro and in vivo tests have shown that the negative myotropic effect caused by the selective vasodilation of this product is weaker than nifedipine, nirendipine, and felodipine; and the vascular selectivity is stronger than that of amlodipine, felodipine, and nitrone Ground level and Laxipine. In addition, this product also has anti-atherosclerosis and end-organ protection effects. This product does not interfere with the normal cardiac excitability and conductivity of patients with hypertension at the therapeutic dose. Animal experiments show that this product has a protective effect on the kidney, and its mechanism may not be related to hemodynamics.

Clinical evaluation of lercanidipine

A randomized double-blind controlled study [1] shows that patients with mild to moderate hypertension given this product 10 or 20 mg, qd can effectively reduce blood pressure (diastolic blood pressure is reduced to 12.0 kPa or 1.3 kPa from baseline), 50% at 10 mg 66%; 86% at 20mg, and its peak ratio (T / P) is higher than 0.8. Studies have shown that the efficacy of 10 mg (qd) of this product for patients with mild to moderate hypertension for more than 4 weeks is at least as good as atenolol 50 mg (qd), candesartan cilexetil 16 mg · d-1, and captopril 25 mg (bid), enalapril 20mg · d-1, hydrochlorothiazide 12.5mg (qd), irbesartan 150mg · d-1 and slow-release nifedipine 25mg (bid) are equivalent to amlodipine 10mg · d-1 . This product is also effective for senile hypertension and simple systolic hypertension. If the dose is increased to 20 or 40 mg · d-1, it can also be used in patients with severe hypertension and patients who are not good at beta-blockers, diuretics or angiotensin-converting enzyme (ACE) inhibitors. In addition, this product is also effective for patients with type 2 diabetes and hypertension, and has no effect on blood sugar.

Lercanidipine pharmacokinetics

This product is a racemate, and the effective part is an S-isomer. After oral administration of 10 or 20 mg to patients with mild to moderate hypertension, their Tmax was 2 to 3 hours, and their Cmax was 1.75 and 4.09 g · L-1, respectively. The AUC was non-linearly related to the dose, indicating that the drug has first-pass metabolism saturation. . Food can increase the absorption of this product. In 12 healthy subjects, a single dose of 20 mg was taken orally, and its Cmax increased from fasted 3.20 g · L-1 to 10.21 g · L-1 after a high-fat meal, so it is recommended to take it after meals. This product quickly distributes and accumulates in the cell membrane lipid bilayer after absorption, and the protein binding rate is higher than 98% [1].

After oral administration, this product is mainly metabolized by CYP3A4 and has a wide range of first-pass effects. About 50% of inactive metabolites are excreted in feces and 44% are excreted in urine. The drug was biphasic, and the terminal elimination half-life (T1 / 2) was 2.8 to 3.7h.

Indications for lercanidipine

In Europe this product is used for various types of hypertension; in the UK it is only used for mild to moderate hypertension.

Lercanidipine adverse reactions

This product is well tolerated. According to the results of a total of about 1,800 patients in 20 clinical trial centers, the incidence of adverse reactions was 11.8%, compared with 7% in the placebo group. The most common adverse reactions were headache, facial appointments, weakness, fatigue, palpitation, and ankle edema. About 3% to 5% of patients discontinued the drug. Clinical observation of 9605 cases shows that the product is well tolerated, of which 7469 patients with mild to moderate hypertension took 10 or 20 mg · d-1 orally for 3 months, the incidence of adverse reactions was 7.6%, and the most common headache was 2.7%) and ankle edema (2.1%). The adverse reactions of this product are mostly mild to moderate, and are related to vasodilation.

Lercanidipine interaction

Synergistic with b-blockers. Attention should be paid to taking digoxin or cimetidine (over 800 mg / day) at the same time. Caution with ketoconazole, itraconazole, erythromycin, fluoxetine, rifampicin, terfenadine, astemizole, cyclosporine, amiodarone, quinidine, certain benzodiazepines , Such as diazepam and midazolam, propranolol and metoprolol. Take with caution with anticonvulsants such as phenytoin or carbamazepine. Grapefruit juice can enhance the effect of this product, and should not be used at the same time. When taking this product, you should abstain from or strictly limit the intake of alcoholic beverages.

Lercanidipine dosage

The recommended dose is 10 mg, qd, which is taken orally at least 15 minutes before a meal, and if necessary, it is increased to 20 mg, qd after 2 weeks.

Lecandipine notes

Disabled for allergic to dihydropyridines; disabled for left ventricular efferent channel block, untreated congestive heart failure, unstable angina pectoris, severe kidney or liver disease, and patients with myocardial infarction within one month ; Pregnant and lactating women, elderly women who have not taken any contraceptive measures; patients under 18 years of age should not take prohibited.

The bioavailability of this product is not affected by age and cirrhosis, but those with severe liver and kidney dysfunction are contraindicated. This product and drug enzyme inhibitors, such as ketoconazole, itraconazole, erythromycin, and fluoxetine; or drug enzyme inducers such as phenytoin, itraconazole, erythromycin, and fluoxetine; and drug enzymes Substrates such as terfenadine, astemizole, cyclosporine, amiodarone, quinidine, diazepam, midazolam, propranolol and metoprolol should be used with caution. In addition, this product can not be combined with grapefruit juice, so as to avoid adverse reactions due to increased blood concentration.