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药品详细

Quinine(奎宁)

化学结构式图
中文名
奎宁
英文名
Quinine
分子式
C20H24N2O2
化学名
(R)-[(1S,2S,4S,5R)-5-ethenyl-1-azabicyclo[2.2.2]octan-2-yl](6-methoxyquinolin-4-yl)methanol
分子量
Average: 324.4168
Monoisotopic: 324.183778022
CAS号
130-95-0
ATC分类
M09A 未知;P01B 未知
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

An alkaloid derived from the bark of the cinchona tree. It is used as an antimalarial drug, and is the active ingredient in extracts of the cinchona that have been used for that purpose since before 1633. Quinine is also a mild antipyretic and analgesic and has been used in common cold preparations for that purpose. It was used commonly and as a bitter and flavoring agent, and is still useful for the treatment of babesiosis. Quinine is also useful in some muscular disorders, especially nocturnal leg cramps and myotonia congenita, because of its direct effects on muscle membrane and sodium channels. The mechanisms of its antimalarial effects are not well understood. [PubChem]

生产厂家
  • Ar holding co inc
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Paintaud G, Alvan G, Berninger E, Gustafsson LL, Idrizbegovic E, Karlsson KK, Wakelkamp M: The concentration-effect relationship of quinine-induced hearing impairment. Clin Pharmacol Ther. 1994 Mar;55(3):317-23. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes Not Available
Substructures Not Available
适应症
药理
Indication For the treatment of malaria and leg cramps
Pharmacodynamics Quinine is used parenterally to treat life-threatening infections caused by chloroquine-resistant Plasmodium falciparum malaria. Quinine acts as a blood schizonticide although it also has gametocytocidal activity against P. vivax and P. malariae. Because it is a weak base, it is concentrated in the food vacuoles of P. falciparum. It is thought to act by inhibiting heme polymerase, thereby allowing accumulation of its cytotoxic substrate, heme. As a schizonticidal drug, it is less effective and more toxic than chloroquine. However, it has a special place in the management of severe falciparum malaria in areas with known resistance to chloroquine.
Mechanism of action The theorized mechanism of action for quinine and related anti-malarial drugs is that these drugs are toxic to the malaria parasite. Specifically, the drugs interfere with the parasite's ability to break down and digest hemoglobin. Consequently, the parasite starves and/or builds up toxic levels of partially degraded hemoglobin in itself.
Absorption 76 - 88%
Volume of distribution
  • 1.43 ± 0.18 L/kg [Healthy Pediatric Controls]
  • 0.87 ± 0.12 L/kg [P. falciparum Malaria Pediatric Patients]
  • 2.5 to 7.1 L/kg [healthy subjects who received a single oral 600 mg dose]
Protein binding Approximately 70%
Metabolism
Hepatic, over 80% metabolized by the liver.

Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

Substrate Enzymes Product
Quinine
3-hydroxyquinine Details
Route of elimination Quinine is eliminated primarily via hepatic biotransformation. Approximately 20% of quinine is excreted unchanged in urine.
Half life Approximately 18 hours
Clearance
  • 0.17 L/h/kg [healthy]
  • 0.09 L/h/kg [patients with uncomplicated malaria]
  • 18.4 L/h [healthy adult subjects with administration of multiple-dose activated charcoal]
  • 11.8 L/h [healthy adult subjects without administration of multiple-dose activated charcoal]
  • Oral cl=0.06 L/h/kg [elderly subjects]
Toxicity Quinine is a documented causative agent of drug induced thrombocytopenia (DIT). Thrombocytopenia is a low amount of platelets in the blood. Quinine induces production of antibodies against glycoprotein (GP) Ib-IX complex in the majority of cases of DIT, or more rarely, the platelet-glycoprotein complex GPIIb-IIIa. Increased antibodies against these complexes increases platelet clearance, leading to the observed thrombocytopenia.
Affected organisms
  • Humans and other mammals
Pathways Not Available
理化性质
Properties
State solid
Experimental Properties
Property Value Source
melting point 57 °C PhysProp
water solubility 500 mg/L (at 15 °C) YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP 3.44 HANSCH,C ET AL. (1995)
logS -2.76 ADME Research, USCD
Predicted Properties
Property Value Source
water solubility 3.34e-01 g/l ALOGPS
logP 2.82 ALOGPS
logP 2.51 ChemAxon
logS -3 ALOGPS
pKa (strongest acidic) 13.89 ChemAxon
pKa (strongest basic) 9.05 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 4 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 45.59 ChemAxon
rotatable bond count 4 ChemAxon
refractivity 94.69 ChemAxon
polarizability 35.96 ChemAxon
药物相互作用
Drug Interaction
Acenocoumarol Quinine, a moderate CYP2C9 inhibitor, may increase the serum concentration of acenocoumarol by decreasing its metabolism via CYP2C9.
Anisindione Quinine may increase the anticoagulant effect of anisindione.
Artemether Quinine may increase the adverse effects of artemether. Combination therapy is contraindicated unless there are no other treatment options.
Astemizole Increased risk of cardiotoxicity and arrhythmias
Atomoxetine The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
Atracurium The quinine derivative increases the effect of the muscle relaxant
Dicumarol Quinine may increase the anticoagulant effect of dicumarol.
Digitoxin Quinine/quinidine increases the effect of digoxin
Digoxin Quinine/quinidine increases the effect of digoxin
Lumefantrine Quinine may increase the adverse effects of lumefantrine. Combination therapy is contraindicated unless there are no other treatment options.
Mesoridazine Increased risk of cardiotoxicity and arrhythmias
Metocurine The quinine derivative increases the effect of the muscle relaxant
Pancuronium The quinine derivative increases the effect of the muscle relaxant
Succinylcholine The quinine derivative increases the effect of the muscle relaxant
Tamoxifen Quinine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
Tamsulosin Quinine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Quinine is initiated, discontinued, or dose changed.
Telithromycin Telithromycin may reduce clearance of Quinine. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Quinine if Telithromycin is initiated, discontinued or dose changed.
Terfenadine Increased risk of cardiotoxicity and arrhythmias
Thioridazine Increased risk of cardiotoxicity and arrhythmias
Thiothixene May cause additive QTc-prolonging effects. Concomitant therapy should be avoided.
Toremifene May cause additive QTc-prolonging effects. Concomitant therapy is contraindicated.
Tramadol Quinine may decrease the effect of Tramadol by decreasing active metabolite production.
Trandolapril May cause additive hypotensive effects. Monitor for changes in blood pressure if Quinine is initiated, discontinued or dose changed.
Tretinoin The moderate CYP2C8 inhibitor, Quinine, may decrease the metabolism and clearance of oral Tretinoin. Monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Quinine is initiated, discontinued to dose changed.
Vecuronium Quinine may increase the neuromuscular blocking action of Vecuronium. Risk of respiratory depression and apnea. Concurrent therapy should be avoided.
Voriconazole Additive QTc prolongation may occur. Concomitant therapy should be avoided.
Vorinostat Additive QTc prolongation may occur. Concomitant therapy should be avoided.
Warfarin Quinine, a moderate CYP2C9 inhibitor, may increase the serum concentration of S-warfarin by decreasing its metabolism via CYP2C9.
Ziprasidone Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Zuclopenthixol Additive QTc-prolonging effects increases risk of cardiac arrhythmias. Concomitant therapy should be avoided.
食物相互作用
  • Take with food to reduce irritation.

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