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药品详细

Nisoldipine(尼索地平)

化学结构式图
中文名
尼索地平
英文名
Nisoldipine
分子式
C20H24N2O6
化学名
3-methyl 5-(2-methylpropyl) 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
分子量
Average: 388.4144
Monoisotopic: 388.16343651
CAS号
63675-72-9
ATC分类
C08C 未知
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

Nisoldipine is a 1,4-dihydropyridine calcium channel blocker. It acts primarily on vascular smooth muscle cells by stabilizing voltage-gated L-type calcium channels in their inactive conformation. By inhibiting the influx of calcium in smooth muscle cells, nisoldipine prevents calcium-dependent smooth muscle contraction and subsequent vasoconstriction. Nisoldipine may be used in alone or in combination with other agents in the management of hypertension.

生产厂家
  • Mylan pharmaceuticals inc
  • Shionogi pharma inc
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Mielcarek J, Grobelny P, Szamburska O: The effect of beta-carotene on the photostability of nisoldipine. Methods Find Exp Clin Pharmacol. 2005 Apr;27(3):167-71. Pubmed
  2. Missan S, Zhabyeyev P, Dyachok O, Jones SE, McDonald TF: Block of cardiac delayed-rectifier and inward-rectifier K+ currents by nisoldipine. Br J Pharmacol. 2003 Nov;140(5):863-70. Epub 2003 Oct 6. Pubmed
  3. Hamilton SF, Houle LM, Thadani U: Rapid-release and coat-core formulations of nisoldipine in treatment of hypertension, angina, and heart failure. Heart Dis. 1999 Nov-Dec;1(5):279-88. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes
  • Nitrobenzenes
Substructures
  • Dihydropyridines
  • Carboxylic Acids and Derivatives
  • Nitrobenzenes
  • Acetates
  • Oxoazaniums
  • Ethers
  • Benzene and Derivatives
  • Nitro compounds
  • Enamines
  • Heterocyclic compounds
  • Aromatic compounds
  • Anilines
适应症
药理
Indication For the treatment of hypertension. It may be used alone or in combination with other antihypertensive agents.
Pharmacodynamics Nisoldipine, a dihydropyridine calcium-channel blocker, is used alone or with an angiotensin-converting enzyme inhibitor, to treat hypertension, chronic stable angina pectoris, and Prinzmetal's variant angina. Nisoldipine is similar to other peripheral vasodilators. Nisoldipine inhibits the influx of extra cellular calcium across the myocardial and vascular smooth muscle cell membranes possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum. The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.
Mechanism of action By deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, Nisoldipine inhibits the influx of extracellular calcium across the myocardial and vascular smooth muscle cell membranes The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.
Absorption Relatively well absorbed into the systemic circulation with 87% of the radiolabeled drug recovered in urine and feces. The absolute bioavailability of nisoldipine is about 5%.
Volume of distribution Not Available
Protein binding 99%
Metabolism
Pre-systemic metabolism in the gut wall, and this metabolism decreases from the proximal to the distal parts of the intestine. Nisoldipine is highly metabolized; 5 major urinary metabolites have been identified. The major biotransformation pathway appears to be the hydroxylation of the isobutyl ester. A hydroxylated derivative of the side chain, present in plasma at concentrations approximately equal to the parent compound, appears to be the only active metabolite and has about 10% of the activity of the parent compound. Cytochrome P450 enzymes are believed to play a major role in the metabolism of nisoldipine. The particular isoenzyme system responsible for its metabolism has not been identified, but other dihydropyridines are metabolized by cytochrome P450 IIIA4.
Route of elimination Although 60-80% of an oral dose undergoes urinary excretion, only traces of unchanged nisoldipine are found in urine.
Half life 7-12 hours
Clearance Not Available
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00381 Nisoldipine Pathway SMP00381
理化性质
Properties
State solid
Experimental Properties
Property Value Source
logP 3.26 MASUMOTO,K ET AL. (1995)
Predicted Properties
Property Value Source
water solubility 5.77e-03 g/l ALOGPS
logP 3.63 ALOGPS
logP 3.06 ChemAxon
logS -4.8 ALOGPS
pKa (strongest basic) 5.32 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 5 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 110.45 ChemAxon
rotatable bond count 8 ChemAxon
refractivity 105.91 ChemAxon
polarizability 39.72 ChemAxon
药物相互作用
Drug Interaction
Conivaptan CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nisoldipine. Avoid concurrent use of nisoldipine with strong inhibitors of CYP3A4, as the combination may lead to substantial increases in nisoldipine concentrations.
Etravirine Nisoldipine, when used concomitantly with etravirine (a strong CYP3A4 inducer), may experience a decrease in serum concentration. It is recommended to avoid concurrent therapy.
Fosphenytoin Phenytoin decreases the efficiency of nisoldipine
Phenytoin Phenytoin decreases the efficiency of nisoldipine
Quinupristin This combination presents an increased risk of toxicity
Telithromycin Telithromycin may reduce clearance of Nisoldipine. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Nisoldipine if Telithromycin is initiated, discontinued or dose changed.
Thiopental The CYP3A4 inducer, Thiopental, may increase the metabolism and clearance of Nisoldipine, a CYP3A4 substrate. Monitor for changes in the therapeutic/adverse effects of Nisoldipine if Thiopental is initiated, discontinued or dose changed.
Tipranavir Tipranavir, co-administered with Ritonavir, may alter the concentration of Nisoldipine. Monitor for efficacy and adverse/toxic effects of Nisoldipine.
Treprostinil Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of nisoldipine by decreasing its metabolism. Concomitant therapy should be avoided.
食物相互作用
  • Do not take with grapefruit juice as this has been shown to interfere with nisoldipine metabolism, resulting in a mean increase in Cmax of about 3-fold (up to about 7-fold) and AUC of almost 2-fold (up to 5-fold).

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