Quinine

Synonyms :
(-)-Quinine, (8S,9R)-Quinine, (R)-(-)-Quinine, (R)-(6-Methoxyquinolin-4-yl)((2S,4S,8R)-8-vinylquinuclidin-2-yl)methanol, 6′-Methoxycinchonidine, Chinin, Chinine, Chininum, Quinina, Quinine

Status : approved

Category

Antimalarials

Therapeutic Classification

ANTIMALARIALS

ANTIPARASITIC PRODUCTS, INSECTICIDES AND REPELLENTS
ANTIPROTOZOALS
ANTIMALARIALS
Analgesics, Non-Narcotic

Description

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]

Used

For the treatment of malaria and leg cramps

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.

Dosage

Form Route Strength
Capsule oral 200 mg
Tablet oral 300 mg
Capsule oral 324 mg
Capsule oral 300 mg

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.

Toxic Effect

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.

Metabolism

Hepatic, over 80% metabolized by the liver.

Absorption

76 – 88%

Half Life

Approximately 18 hours

Protein Binding

Approximately 70%

Elimination Route

Quinine is eliminated primarily via hepatic biotransformation. Approximately 20% of quinine is excreted unchanged in urine.

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]

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]

Chemical Classification

This compound belongs to the class of organic compounds known as cinchona alkaloids. These are alkaloids structurally characterized by the presence of the cinchonan skeleton, which consists of a quinoline linked to an azabicyclo[2.2.2]octane moiety.

Cinchona alkaloids

Organic compounds

Alkaloids and derivatives

Cinchona alkaloids

Salt : Quinine Hydrochloride

Chemical Name

(-)-Quinine

Brands

name Dosage form Country
Apo-quinine Capsules capsule Canada
Apo-quinine Capsules capsule Canada
Jamp-quinine capsule Canada
Jamp-quinine capsule Canada
Pro-quinine – 200 capsule Canada
Pro-quinine – 300 capsule Canada
Qualaquin capsule US
Qualaquin capsule US
Qualaquin capsule US
Quinine – Odan tablet Canada
Quinine – Odan capsule Canada
Quinine – Odan capsule Canada
Quinine Sulfate capsule US
Quinine Sulfate capsule US
Quinine Sulfate capsule US
Quinine Sulfate capsule US
Quinine Sulfate capsule Canada
Quinine Sulfate capsule Canada
Quinine Sulfate capsule US
Quinine Sulfate capsule US
Quinine Sulfate Cap 200mg capsule Canada
Quinine Sulfate Cap 200mg capsule Canada
Quinine Sulfate Cap 300mg capsule Canada
Quinine Sulfate Cap 300mg capsule Canada
Quinine Sulfate Capsules 200mg capsule Canada
Quinine Sulfate Capsules 300mg capsule Canada
Teva-quinine capsule Canada
Teva-quinine capsule Canada

Drug Drug Interactions

  •  Acenocoumarol  : May enhance the anticoagulant effect of Vitamin K Antagonists.
  •  Acetohexamide  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Acetylsalicylic acid  : May enhance the hypoglycemic effect of Blood Glucose Lowering Agents.
  •  Afatinib  : P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib.
  •  Alogliptin  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Aluminum hydroxide  : Antacids may decrease the serum concentration of Quinine.
  •  Aminophylline  : May increase the serum concentration of Theophylline Derivatives.
  •  Amodiaquine  : CYP2C8 Inhibitors may increase the serum concentration of Amodiaquine.
  •  Aprepitant  : May increase the serum concentration of CYP3A4 Substrates.
  •  Artemether  : May enhance the adverse/toxic effect of Antimalarial Agents.
  •  Atorvastatin  : May increase the serum concentration of HMG-CoA Reductase Inhibitors.
  •  Atracurium besylate  : May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents.
  •  Azithromycin  : Macrolide Antibiotics may increase the serum concentration of Quinine.
  •  Bosentan  : May decrease the serum concentration of CYP3A4 Substrates.
  •  Bosentan  : CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Bosentan.
  •  Bosutinib  : P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bosutinib.
  •  Brentuximab vedotin  : P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Brentuximab vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased.
  •  Brexpiprazole  : CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Brexpiprazole.
  •  Canagliflozin  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Carbamazepine  : May decrease the serum concentration of Quinine. Quinine may increase the serum concentration of Carbamazepine.
  •  Carvedilol  : CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Carvedilol. Specifically, concentrations of the S-carvedilol enantiomer may be increased.
  •  Chlorpropamide  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Cimetidine  : May increase the serum concentration of Quinine.
  •  Cisatracurium besylate  : May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents.
  •  Clarithromycin  : Macrolide Antibiotics may increase the serum concentration of Quinine.
  •  Codeine  : CYP2D6 Inhibitors (Moderate) may diminish the therapeutic effect of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine.
  •  Colchicine  : P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased.
  •  Conivaptan  : May increase the serum concentration of CYP3A4 Substrates.
  •  Dabigatran etexilate  : P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran etexilate.
  •  Dabrafenib  : May decrease the serum concentration of CYP3A4 Substrates.
  •  Deferasirox  : May decrease the serum concentration of CYP3A4 Substrates.
  •  Digoxin  : Quinine may increase the serum concentration of Digoxin.
  •  Dihydrotestosterone  : May enhance the hypoglycemic effect of Blood Glucose Lowering Agents.
  •  Dronabinol  : CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Dronabinol.
  •  Dronabinol  : CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Tetrahydrocannabinol.
  •  Dyphylline  : May increase the serum concentration of Theophylline Derivatives.
  •  Edoxaban  : P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Edoxaban.
  •  Erythromycin  : Macrolide Antibiotics may increase the serum concentration of Quinine.
  •  Everolimus  : P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus.
  •  Fesoterodine  : CYP2D6 Inhibitors may increase serum concentrations of the active metabolite(s) of Fesoterodine.
  •  Fosaprepitant  : May increase the serum concentration of CYP3A4 Substrates.
  •  Fosphenytoin  : May decrease the serum concentration of Quinine.
  •  Gliclazide  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Glimepiride  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Gliquidone  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Glyburide  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Halofantrine  : Quinine may enhance the adverse/toxic effect of Halofantrine. Quinine may increase the serum concentration of Halofantrine.
  •  Idelalisib  : May increase the serum concentration of CYP3A4 Substrates.
  •  Insulin Aspart  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Insulin Detemir  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Insulin Glargine  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Insulin Glulisine  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Insulin Lispro  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Insulin Regular  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Insulin, isophane  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Ivabradine  : May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents.
  •  Ivacaftor  : May increase the serum concentration of CYP3A4 Substrates.
  •  Ledipasvir  : P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ledipasvir.
  •  Linagliptin  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Lopinavir  : May decrease the serum concentration of Quinine. This effect has been seen with Lopinavir/ritonavir. The individual contributions of Lopinavir and ritonavir to this effect are unclear.
  •  Lovastatin  : May increase the serum concentration of HMG-CoA Reductase Inhibitors.
  •  Luliconazole  : May increase the serum concentration of CYP3A4 Substrates.
  •  Lumefantrine  : Antimalarial Agents may enhance the adverse/toxic effect of Lumefantrine.
  •  Magnesium hydroxide  : Antacids may decrease the serum concentration of Quinine.
  •  Magnesium oxide  : May decrease the serum concentration of Quinine.
  •  Mefloquine  : Quinine may enhance the adverse/toxic effect of Mefloquine. Specifically, the risk for QTc-prolongation and the risk for convulsions may be increased. Mefloquine may increase the serum concentration of Quinine.
  •  Metformin  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Metoprolol  : CYP2D6 Inhibitors may increase the serum concentration of Metoprolol.
  •  Mifepristone  : May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents.
  •  Mitotane  : May decrease the serum concentration of CYP3A4 Substrates.
  •  Naloxegol  : P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naloxegol.
  •  Nebivolol  : CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Nebivolol.
  •  Netupitant  : May increase the serum concentration of CYP3A4 Substrates.
  •  Nitric Oxide  : May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Combinations of these agents may increase the likelihood of significant methemoglobinemia.
  •  Oxandrolone  : May enhance the hypoglycemic effect of Blood Glucose Lowering Agents.
  •  Palbociclib  : May increase the serum concentration of CYP3A4 Substrates.
  •  Pancuronium  : May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents.
  •  Pazopanib  : P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Pazopanib.
  •  Pegvisomant  : May enhance the hypoglycemic effect of Blood Glucose Lowering Agents.
  •  Phenobarbital  : Quinine may increase the serum concentration of Phenobarbital. Phenobarbital may decrease the serum concentration of Quinine.
  •  Phenytoin  : May decrease the serum concentration of Quinine.
  •  Prilocaine  : Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Prilocaine. Combinations of these agents may increase the likelihood of significant methemoglobinemia.
  •  Prucalopride  : P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of prucalopride.
  •  Repaglinide  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Rifampicin  : May decrease the serum concentration of Quinine.
  •  Rifaximin  : P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Rifaximin.
  •  Ritonavir  : May decrease the serum concentration of Quinine. This effect has been seen with lopinavir/ritonavir. The individual contributions of lopinavir and ritonavir to this effect are unclear. Quinine may increase the serum concentration of Ritonavir. Ritonavir may increase the serum concentration of Quinine.
  •  Rocuronium  : May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents.
  •  Salicylate-sodium  : May enhance the hypoglycemic effect of Blood Glucose Lowering Agents.
  •  Saxagliptin  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Silodosin  : P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin.
  •  Siltuximab  : May decrease the serum concentration of CYP3A4 Substrates.
  •  Simeprevir  : May increase the serum concentration of CYP3A4 Substrates.
  •  Simvastatin  : May increase the serum concentration of HMG-CoA Reductase Inhibitors.
  •  Sodium bicarbonate  : Alkalinizing Agents may increase the serum concentration of Quinine.
  •  Sodium Nitrite  : Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Sodium Nitrite. Combinations of these agents may increase the likelihood of significant methemoglobinemia.
  •  Spiramycin  : Macrolide Antibiotics may increase the serum concentration of Quinine.
  •  Stiripentol  : May increase the serum concentration of CYP3A4 Substrates.
  •  Succinylcholine  : May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents.
  •  Sulfisoxazole  : Macrolide Antibiotics may increase the serum concentration of Quinine.
  •  Tamoxifen  : CYP2D6 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Tamoxifen. Specifically, CYP2D6 inhibitors may decrease the metabolic formation of highly potent active metabolites.
  •  Telithromycin  : Macrolide Antibiotics may increase the serum concentration of Quinine.
  •  Testosterone  : May enhance the hypoglycemic effect of Blood Glucose Lowering Agents.
  •  Tetracycline  : May increase the serum concentration of Quinine.
  •  Theophylline  : May increase the serum concentration of Theophylline Derivatives.
  •  Thioridazine  : CYP2D6 Inhibitors may increase the serum concentration of Thioridazine.
  •  Tocilizumab  : May decrease the serum concentration of CYP3A4 Substrates.
  •  Tolbutamide  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Topotecan  : P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan.
  •  Tramadol  : CYP2D6 Inhibitors (Moderate) may diminish the therapeutic effect of Tramadol. These CYP2D6 inhibitors may prevent the metabolic conversion of Tramadol to its active metabolite that accounts for much of its opioid-like effects.
  •  Vecuronium  : May enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents.
  •  Vildagliptin  : May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents.
  •  Warfarin  : May enhance the anticoagulant effect of Vitamin K Antagonists.

Food Interactions

  • Take with food to reduce irritation.

Calculated Property

kind Value Source
logP 2.82 ALOGPS
logS -3 ALOGPS
Water Solubility 3.34e-01 g/l ALOGPS
logP 2.51 ChemAxon
IUPAC Name (R)-[(1S,2S,4S,5R)-5-ethenyl-1-azabicyclo[2.2.2]octan-2-yl](6-methoxyquinolin-4-yl)methanol ChemAxon
Traditional IUPAC Name quinine ChemAxon
Molecular Weight 324.4168 ChemAxon
Monoisotopic Weight 324.183778022 ChemAxon
SMILES [H][C@]1(C[C@@H]2CC[N@]1C[C@@H]2C=C)[C@H](O)C1=CC=NC2=CC=C(OC)C=C12 ChemAxon
Molecular Formula C20H24N2O2 ChemAxon
InChI InChI=1S/C20H24N2O2/c1-3-13-12-22-9-7-14(13)10-19(22)20(23)16-6-8-21-18-5-4-15(24-2)11-17(16)18/h3-6,8,11,13-14,19-20,23H,1,7,9-10,12H2,2H3/t13-,14-,19-,20+/m0/s1 ChemAxon
InChIKey InChIKey=LOUPRKONTZGTKE-WZBLMQSHSA-N ChemAxon
Polar Surface Area (PSA) 45.59 ChemAxon
Refractivity 94.69 ChemAxon
Polarizability 35.96 ChemAxon
Rotatable Bond Count 4 ChemAxon
H Bond Acceptor Count 4 ChemAxon
H Bond Donor Count 1 ChemAxon
pKa (strongest acidic) 13.89 ChemAxon
pKa (strongest basic) 9.05 ChemAxon
Physiological Charge 1 ChemAxon
Number of Rings 4 ChemAxon
Bioavailability 1 ChemAxon
Rule of Five 1 ChemAxon
Ghose Filter 1 ChemAxon
MDDR-Like Rule 0 ChemAxon

Affected organism

Humans and other mammals

Target within organism

  • Fe(II)-protoporphyrin IX : in Plasmodium falciparum
  • Platelet glycoprotein IX : in Human
  • Intermediate conductance calcium-activated potassium channel protein 4 : in Human