Quinine

Pharmaceuticals -> Listed in ZINC15

Pharmaceuticals -> Used in Switzerland

log Kow = 3.44

2.6

Triboluminescent, orthorhombic needles from absolute alcohol

Bulky, white, amorphous powder or crystalline alkaloid

CRYSTALS TURN BROWN ON EXPOSURE TO AIR

In water, 500 mg/L at 15 °C

1 g dissolves in: 1900 mL water, 760 mL boiling water

1 g dissolves in: 80 mL benzene (18 mL at 50 °C), 1.2 mL chloroform, 250 mL dry ether, 20 mL glycerol, 0.8 mL alcohol, 1900 mL of 10% ammonia water; almost insoluble in petroleum ether

Soluble in ether, chloroform, carbon disulfide, glycerol, alkalies, and acids (with formation of salts)

Sol in pyrimidine

Breast Feeding; Lactation; Anti-infective Agents; Antiparasitic Agents; Antimalarials; Antiprotozoal Agents; Foodborne Diseases; Glucosephosphate Dehydrogenase Deficiency

Antimalarial medicines > For curative treatment

Danger

H302 (22.9%): Harmful if swallowed [Warning Acute toxicity, oral]

P233, P260, P261, P264, P264+P265, P270, P271, P272, P280, P284, P301+P317, P302+P352, P304+P340, P305+P351+P338, P321, P330, P332+P317, P333+P317, P337+P317, P342+P316, P362+P364, P403, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 201 reports by companies from 10 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Warning

H302: Harmful if swallowed [Warning Acute toxicity, oral]

Chemical: Cinchonan-9-ol, 6'-methoxy-, (8.alpha.,9R)-

Status: Active Update: 08-09-2020 https://echa.europa.eu/registration-dossier/-/registered-dossier/16572

Cinchonan-9-ol, 6'-methoxy-, (8.alpha.,9R)-: Does not have an individual approval but may be used under an appropriate group standard

Quinine, as the hydrochloride salt or sulfate salt, may be safely used in food in accordance with the following conditions: Use: In carbonated beverages as a flavor. Limitations: Not to exceed 83 parts per million, as quinine. Label shall bear a prominent declaration of the presence of quinine either by the use of the word "quinine" in the name of the article or through a separate declaration.

Any product that bears labeling claims that it "helps stop or reduce the cigarette urge," "helps break the cigarette habit," "helps stop or reduce smoking," or similar claims is a smoking deterrent drug product. ... Quinine ascorbate ... /has/ been present as /an/ ingredients in such drug products. There is a lack of adequate data to establish general recognition of the safety and effectiveness ... for OTC use as a smoking deterrent. Based on evidence currently available, any OTC drug product containing ingredients offered for use as a smoking deterrent cannot be generally recognized as safe and effective. /Quinine ascorbate/

Drug products containing certain active ingredients offered over-the-counter (OTC) for certain uses. A number of active ingredients have been present in OTC drug products for various uses, as described below. However, based on evidence currently available, there are inadequate data to establish general recognition of the safety and effectiveness of these ingredients for the specified uses: quinine is included in internal analgesic drug products.

Quinine sulfate alone or in combination with vitamin E has been present in over-the-counter (OTC) drug products for the treatment and/or prevention of nocturnal leg muscle cramps, i.e., a condition of localized pain in the lower extremities usually occurring in middle life and beyond with no regular pattern concerning time or severity. There is a lack of adequate data to establish general recognition of the safety and effectiveness of quinine sulfate, vitamin E, or any other ingredients for OTC use in the treatment and/or prevention of nocturnal leg muscle cramps. In the doses used to treat or prevent this condition, quinine sulfate has caused adverse events such as transient visual and auditory disturbances, dizziness, fever, nausea, vomiting, and diarrhea. Quinine sulfate may cause unpredictable serious and life-threatening hypersensitivity reactions requiring medical intervention and hospitalization; fatalities have been reported. The risk associated with use of quinine sulfate, in the absence of evidence of its effectiveness, outweighs any potential benefit in treating and/or preventing this benign, self-limiting condition. Based upon the adverse benefit-to-risk ratio, any drug product containing quinine or quinine sulfate cannot be considered generally recognized as safe for the treatment and/or prevention of nocturnal leg muscle cramps.

For more FDA Requirements (Complete) data for QUININE (6 total), please visit the HSDB record page.

MANKU MS, HORROBIN DE; LANCET 2(7995) 1115-1117 (1976). A REVIEW WITH 84 REF ON CHLOROQUINE, QUININE, PROCAINE, TRICYCLIC ANTIDEPRESSANTS, QUINIDINE & METHYLXANTHINES AS PROSTAGLANDIN AGONISTS & ANTAGONISTS.

Bologa M et al; Drugs and Chemicals Most Commonly Used by Pregnant Women. Maternal-Fetal Toxicology: a Clinicians' Guide: 29-51 (1990). Factors affecting transplacental DNA damage were examined. Timed pregnant mice or monkeys were given a single dose of carcinogen on different gestation days, sacrificed 1-50 days later, and analyzed for DNA adducts by the (32)P postlabeling assay. The following results were obtained: (1) The chemical types of carcinogen determine the fetal and fetal/maternal adduct levels and whether there is a gestation stage dependency in DNA binding. In the mice, 4-nitroquinoline 1-oxide bound to fetal DNA at low levels, without organotropism (in contrast to maternal tissues), and without a gestation stage dependency. Benzo(a)pyrene bound to fetal DNA at high levels, with slight organ preference (as for adults), with strong gestation stage dependency, and peaking before parturition. The ontogenesis of benzo(a)pyrene DNA adduct levels exhibited organ specificity. Safrole preferentially bound to fetal liver (as for adults) with strong gestation stage specificity. (2) The maternal and fetal Ah genotype affects the types and amounts of 3-methylcholanthrene DNA adducts in the mothers, placenta and fetuses. (3) Benzo(a)pyrene produces the same type and comparable amounts of adducts in fetal monkeys and mice during gestation. (4) Benzo(a)pyrene adducts persist in fetal mouse embryos and monkey tissues for at least 1/3 of gestation. (5) All carcinogens tested bound ubiquitously to all fetal and possible embryonic, DNA with levels exhibiting little relationship to placental levels. (6) Fetal adduct levels varied from 0.05-2 fold of maternal levels depending on the carcinogen tested. Thus, fetal competence in metabolism of a specific carcinogen is a determining factor for transplacental DNA damage. Placental adduct levels are a qualitative, but not a quantitative, indicator of fetal exposure.

Panisko DM, Keystone JS; Treatment of Malaria--1990. Drugs 39S (Feb): 160-89 (1990). A review of the treatment of malaria is presented, including the chemistry, pharmacokinetics, mechanisms of action, resistance, and toxicity of quinine. The distribution of malaria and patterns of resistance are examined.

Acute Tox. 4 (22.9%)

Acute toxicity - category 4

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.

Advice for firefighters: Wear self contained breathing apparatus for fire fighting if necessary.

Store at 20 deg to 25 °C (68 deg to 77 °F).

Conditions for safe storage, including any incompatibilities: Keep container tightly closed in a dry and well-ventilated place. Light sensitive.

Accidental Release Measures. Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapours, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Do not let product enter drains. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.

SRP: At the time of review, regulatory criteria for small quantity disposal are subject to significant revision, however, household quantities of waste pharmaceuticals may be managed as follows: Mix with wet cat litter or coffee grounds, double bag in plastic, discard in trash.

Waste treatment methods. Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber. Contaminated packaging: Dispose of as unused product.

Precautions for safe handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed.

Appropriate engineering controls: Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.

Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.

SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.

Eye/face protection: Face shield and safety glasses Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).

Skin protection: Handle with gloves.

Body Protection: Complete suit protecting against chemicals, The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.

Respiratory protection: For nuisance exposures use type P95 (US) or type P1 (EU EN 143) particle respirator.For higher level protection use type OV/AG/P99 (US) or type ABEK-P2 (EU EN 143) respirator cartridges. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

Cinchona alkaloids, including quinine, may depress the hepatic synthesis of vitamin K-dependent coagulation factors, and the resulting hypoprothrombinemic effect may enhance the action of warfarin and other oral anticoagulants. In patients receiving these anticoagulants and concomitant therapy with quinine, the prothrombin time (PT), partial thromboplastin time (PTT), or international normalized ratio (INR) should be closely monitored as indicated.

The pharmacokinetics of quinine was investigated in patients with acute Falciparum malaria treated with quinine alone or in the presence of doxycycline. Twenty six patients divided into two groups of equal number were enrolled in the study. In the absence of doxycycline, the volume of distribution of quinine (mean + or - standard deviation) was estimated to be 1.32 + or - 0.32 l/kg, and its clearance was 0.125 + or - 0.47 l/hr/kg, which was only in partial agreement with previously published data. No effect of doxycycline on the pharmacokinetics of quinine was observed.

Quinine is a substrate for and an inhibitor of P-glycoprotein, and has the potential to affect the transport of drugs that are P-glycoprotein substrates.

Quinine may affect the pharmacokinetics of drugs that are CYP2D6 substrates. There is evidence that quinine decreased the metabolism of desipramine (a CYP2D6 substrate) in patients who were extensive CYP2D6 metabolizers, but had no effect in patients who were poor CYP2D6 metabolizers. Although low doses of quinine (80-400 mg) did not significantly affect the pharmacokinetics of some other CYP2D6 substrates (debrisoquine, dextromethorphan, methoxyphenamine), it is possible that higher quinine doses (600 mg or more) may inhibit the metabolism of these and other CYP2D6 substrates (e.g., flecainide, metoprolol, paroxetine). Patients receiving quinine concomitantly with drugs that are CYP2D6 substrates should be monitored closely for adverse effects of these drugs.

For more Interactions (Complete) data for QUININE (24 total), please visit the HSDB record page.

It is usual for quinine in therapeutic doses to cause cinchonism; in rare cases, it may even cause death (usually by pulmonary edema). Quinine can worsen hemoglobinuria, myasthenia gravis and optic neuritis. It can cause paralysis if accidentally injected into a nerve, and is extremely toxic in overdose[Wikipedia]

There is little evidence that chronic quinine therapy is associated with elevations in serum enzymes, although it has not been carefully assessed. However, there have been several reports of acute hypersensitivity reactions to quinine that include hepatic involvement. The reactions usually arise after 1 to 2 weeks of therapy, but can appear within 24 hours of restarting quinine or with rechallenge. The clinical features are marked by fatigue, nausea, vomiting, diffuse muscle aches, arthralgias and high fever. Blood testing at an early stage shows increases in serum aminotransferase and alkaline phosphatase levels as well as mild jaundice, which can deepen for a few days even after stopping quinine. The pattern of serum enzymes elevations is typically cholestatic or mixed. Rash is uncommon and eosinophilia is not typical, despite the presence of other signs of hypersensitivity (fever, arthralgias). Autoantibodies are not typically found. Liver biopsies usually show mild injury and small epithelioid granulomas, as are typically found in many organs during systemic hypersensitivity reactions. A similar clinical signature of liver injury occurs with quinidine, an optical isomer of quinine that is used predominantly as an antiarrhythmic.

EXPERIMENTAL: Quinine readily crosses the placenta is distributed into milk. In one study, quinine concentrations in placental cord blood and breast milk were approximately 32 and 31%, respectively, of maternal plasma quinine concentrations. The estimated total amount of quinine distributed into breast milk daily was less than 2-3 mg.

EXPERIMENTAL: Quinine is excreted into breast milk. Following 300 and 640 mg oral doses in six patients, the drug was detectable in milk up to 23 hours after a dose, with concentrations ranging from trace to 2.2 ug/mL.

IDENTIFICATION AND USE: Quinine is a bulky, white, amorphous powder or crystalline alkaloid, used as medication: non-narcotic analgesics; antimalarial; central muscle relaxants. It is also used as flavor in carbonated beverages. HUMAN EXPOSURE AND TOXICITY: Serious hypersensitivity reactions, including anaphylactic shock, anaphylactoid reactions, urticaria, serious skin rashes, angioedema, facial edema, bronchospasm, and pruritus, have been reported with quinine. In addition, thrombocytopenia, hemolytic uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP), immune thrombocytopenic purpura, blackwater fever, disseminated intravascular coagulation, leukopenia, neutropenia, granulomatous hepatitis, and acute interstitial nephritis have been reported and may also be due to hypersensitivity reactions to the drug. Potentially fatal cardiac arrhythmias, including torsades de pointes and ventricular fibrillation, have been reported rarely during quinine therapy. At least 1 case of fatal ventricular arrhythmia has been reported in a geriatric patient with preexisting prolonged QT interval treated with IV quinine sulfate for Plasmodium falciparum malaria. Visual impairment can range from blurred vision and defective color perception, to visual field constriction and permanent blindness. Cinchonism occurs in virtually all patients with quinine overdose. There have been a large number of case reports of malformations following quinine ingestion in human pregnancy. Many of these pregnancies involved large doses of quinine used as an abortifacient. The most frequently reported abnormality following quinine exposure during early pregnancy is hypoplasia of the auditory nerve with resultant deafness. Other major malformations involving most organ systems have been reported also. However, the Perinatal Collaborative Study reported no association between first trimester exposure to quinine and birth defects. In general, there has been no proven association between quinine at doses used for malarial prophylaxis and an increased risk of malformations. Third trimester exposure to quinine does not appear to adversely affect uterine contractility. However, an increase in insulin secretion associated with hypoglycemia has been reported. Therefore, monitoring of blood or serum glucose levels during quinine therapy is advisable. Although the United States Food and Drug Administration banned its use for nocturnal leg cramps due to lack of safety and efficacy, quinine is widely available in beverages including tonic water and bitter lemon. Numerous anecdotal reports suggest that products containing quinine may produce neurological complications, including confusion, altered mental status, seizures, and coma, particularly in older women. ANIMAL STUDIES: Rabbits given 20 to 100 mg quinine hydrochloride/kg intravenously or intramuscularly 3 times a week for 10 weeks have been reported to show no ophthalmoscopic or histologic abnormalities in the fundus or optic nerve, and /another study/ similarly found no abnormality in most rabbits injected intraperitoneally with 10 mg/kg/day for 21 to 27 days showed degeneration of rods and cones and vacuoles in the retinal ganglion cells. In animal developmental studies conducted in multiple animal species, pregnant animals received quinine by the subcutaneous or intramuscular route at dose levels similar to the maximum recommended human dose based on body surface area (BSA) comparisons. There were increases in fetal death in utero in rabbits at maternal doses = 100 mg/kg/day and in dogs at = 15 mg/kg/day cochlea at maternal doses of 200 mg/kg corresponding to a dose level of approximately 1.4 times the MRHD based on BSA comparison. There were no teratogenic findings in rats at maternal doses up to 300 mg/kg/day and in monkeys at doses up to 200 mg/kg/day corresponding to doses approximately 1 and 2 times the MRHD respectively based on BSA comparisons. Quinine produces testicular toxicity in mice at a single intraperitoneal dose of 300 mg/kg, and in rats at an intramuscular dose of 10 mg/kg/day, 5 days/week, for 8 weeks. The findings include atrophy or degeneration of the seminiferous tubules, decreased sperm count and motility, and decreased testosterone levels in the serum and testes. Genotoxicity studies of quinine were positive in the Ames bacterial mutation assay with metabolic activation and in the sister chromatid exchange assay in mice. The sex-linked recessive lethal test performed in Drosophila, the in vivo mouse micronucleus assay, and the chromosomal aberration assay in mice and Chinese hamsters were negative.

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.

Quinone is found in the bark of cinchona species (Rubiaceae)(1) native to Indonesia and Bolivia(2).

QUININE IS CHIEF ALKALOID OF CINCHONA, THE BARK OF CINCHONA TREE INDIGENOUS TO CERTAIN REGIONS OF SOUTH AMERICA ... BARK IS ALSO CALLED PERUVIAN, JESUIT'S OR CARDINAL'S BARK.

/HUMAN EXPOSURE STUDIES/ Following a double-blind, four-way crossover design, 32 healthy volunteers (20 males and 12 females) each consumed lactose placebo, or 80, 120 or 160 mg quinine HCl daily for 21 days. Before dosing and at regular intervals during dosing, blood and urine samples were collected and analysed for quinine HCl. Electrocardiography, heart rate, blood pressure, audiometry, peripheral field, funduscopy, colour vision, visual acuity, electronystagmography (ENG) and test for optokinetic nystagmus were all evaluated before dosing and at selected times during dosing. The results showed that daily consumption of up to 80 mg quinine HCl did not significantly alter physiological, ophthalmic or audiometric responses. ENG determination showed that 12.5% of volunteers given lactose placebo or 80 mg quinine HCl exhibited at least one transitory period of ocular motor oscillations. This phenomenon was observed in 18.8% (P < 0.05) of volunteers with a daily intake of 120 mg quinine HCl or more. However, there was not a significant dose-related correlation between nystagmus and daily intake of quinine HCl. Five volunteers consuming lactose placebo displayed an aberrant ocular flutter that decreased significantly (P < 0.05) as the daily intake of quinine HCl increased. One volunteer showed a change in perception of red/green colour vision after taking 160 mg quinine HCl for 21 days. This study demonstrated that the no-untoward-effect level of quinine HCl is at least 80 mg/day.

/HUMAN EXPOSURE STUDIES/ In 4 healthy adults receiving digoxin (0.5-0.75 mg daily) concomitantly with quinine (750 mg daily), a 33% increase in mean steady-state AUC of digoxin and a 35% reduction in steady-state biliary clearance of digoxin were observed compared to that observed in adults receiving digoxin alone. Plasma concentrations of digoxin should be closely monitored in patients receiving quinine and the digoxin dose adjusted, as necessary.

/HUMAN EXPOSURE STUDIES/ In a published study in 5 men receiving 600 mg of quinine TID for one week, sperm motility was decreased and percent sperm with abnormal morphology was increased; sperm count and serum testosterone were unaffected.

/HUMAN EXPOSURE STUDIES/ Audiometric changes following quinine administration were studied in healthy Caucasian subjects and patients suffering from falciparum malaria disease. Quinine-dihydrochloride was administered intravenously as a single dose of 300 mg to 12 healthy subjects and as multiple doses of 600 mg in 4 hr every 8 hr in 10 Plasmodium falciparum malaria patients. The hearing function was monitored by conventional and high frequency audiometry. In nine healthy subjects hearing loss was documented at 2-4 hr after infusion of Quinine-dihydrochloride at a mean maximal plasma quinine concentration of only 2 mg/L. In one healthy subject a persistent loss occurred of 20 dB at 14 kHz in one ear. In all malaria patients severe hearing losses and adverse effects related to ototoxicity were documented, but all the audiograms had returned to normal after 1 week and side effects disappeared. This study has shown that ototoxicity induced by quinine is almost completely reversible in healthy volunteers and in malaria patients.

For more Human Toxicity Excerpts (Complete) data for QUININE (28 total), please visit the HSDB record page.

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

quinine

DILI Positive

Oral

DOI:10.1016/j.drudis.2019.09.022

Quinine, as the hydrochloride salt or sulfate salt, may be safely used in food in accordance with the following conditions: Use: In carbonated beverages as a flavor. Limitations: Not to exceed 83 parts per million, as quinine. Label shall bear a prominent declaration of the presence of quinine either by the use of the word "quinine" in the name of the article or through a separate declaration.

Any product that bears labeling claims that it "helps stop or reduce the cigarette urge," "helps break the cigarette habit," "helps stop or reduce smoking," or similar claims is a smoking deterrent drug product. ... Quinine ascorbate ... /has/ been present as /an/ ingredients in such drug products. There is a lack of adequate data to establish general recognition of the safety and effectiveness ... for OTC use as a smoking deterrent. Based on evidence currently available, any OTC drug product containing ingredients offered for use as a smoking deterrent cannot be generally recognized as safe and effective. /Quinine ascorbate/

Drug products containing certain active ingredients offered over-the-counter (OTC) for certain uses. A number of active ingredients have been present in OTC drug products for various uses, as described below. However, based on evidence currently available, there are inadequate data to establish general recognition of the safety and effectiveness of these ingredients for the specified uses: quinine is included in internal analgesic drug products.

Quinine sulfate alone or in combination with vitamin E has been present in over-the-counter (OTC) drug products for the treatment and/or prevention of nocturnal leg muscle cramps, i.e., a condition of localized pain in the lower extremities usually occurring in middle life and beyond with no regular pattern concerning time or severity. There is a lack of adequate data to establish general recognition of the safety and effectiveness of quinine sulfate, vitamin E, or any other ingredients for OTC use in the treatment and/or prevention of nocturnal leg muscle cramps. In the doses used to treat or prevent this condition, quinine sulfate has caused adverse events such as transient visual and auditory disturbances, dizziness, fever, nausea, vomiting, and diarrhea. Quinine sulfate may cause unpredictable serious and life-threatening hypersensitivity reactions requiring medical intervention and hospitalization; fatalities have been reported. The risk associated with use of quinine sulfate, in the absence of evidence of its effectiveness, outweighs any potential benefit in treating and/or preventing this benign, self-limiting condition. Based upon the adverse benefit-to-risk ratio, any drug product containing quinine or quinine sulfate cannot be considered generally recognized as safe for the treatment and/or prevention of nocturnal leg muscle cramps.

For more FDA Requirements (Complete) data for QUININE (6 total), please visit the HSDB record page.

P - Antiparasitic products, insecticides and repellents

P01BC01

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.

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.

Quinine has a local anesthetic action and analgesic, antipyretic, and oxytocic effects. Quinine also has cardiovascular effects similar to those of quinidine.

Approximately 18 hours

Compared with administration of quinine alone, administration of a single 600-mg dose of quinine sulfate in healthy individuals who were receiving ritonavir (200 mg every 12 hours) resulted in an increased quinine mean elimination half-life (11.2 hours versus 13.4 hours).

The plasma elimination half-life of quinine reportedly averages 8-21 hours in adults with malaria and 7-12 hours in healthy or convalescing adults.

The steady-state pharmacokinetics after a quinine sulfate dosage of 648 mg 3 times daily for 7 days were similar in healthy geriatric adults 65-78 years of age and healthy younger adults 20-39 years of age; however, the mean elimination half-life was 24 hours in the geriatric individuals compared with 20 hours in the younger adults.

In children 1-12 years of age, the plasma elimination half-life of quinine reportedly averages 11-12 hours in those with malaria and 6 hours in those convalescing from the disease.

At toxic levels elimination half life is reported to be 26.5 + or - 5.8 hrs.

Hepatic, over 80% metabolized by the liver.

In vitro studies using human liver microsomes and recombinant P450 enzymes have shown that quinine is metabolized mainly by CYP3A4. Depending on the in vitro experimental conditions, other enzymes, including CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP2E1 were shown to have some role in the metabolism of quinine.

Quinine is metabolized almost exclusively via hepatic oxidative cytochrome P450 (CYP) pathways, resulting in four primary metabolites, 3-hydroxyquinine, 2'-quinone, O-desmethylquinine, and 10,11-dihydroxydihydroquinine. Six secondary metabolites result from further biotransformation of the primary metabolites. The major metabolite, 3-hydroxyquinine, is less active than the parent drug.

Quinine has known human metabolites that include 3-Ethenyl-6-[hydroxy-(6-methoxyquinolin-4-yl)methyl]-1-azabicyclo[2.2.2]octan-3-ol.

Hepatic, over 80% metabolized by the liver. Route of Elimination: Quinine is eliminated primarily via hepatic biotransformation. Approximately 20% of quinine is excreted unchanged in urine. Half Life: Approximately 18 hours

A7V27PHC7A

QUININE

Established Pharmacologic Class [EPC] - Antimalarial

Quinine is an Antimalarial.

QUININE

Antimalarial [EPC]

Agents used in the treatment of malaria. They are usually classified on the basis of their action against plasmodia at different stages in their life cycle in the human. (From AMA, Drug Evaluations Annual, 1992, p1585)

A heterogeneous group of drugs used to produce muscle relaxation, excepting the neuromuscular blocking agents. They have their primary clinical and therapeutic uses in the treatment of muscle spasm and immobility associated with strains, sprains, and injuries of the back and, to a lesser degree, injuries to the neck. They have been used also for the treatment of a variety of clinical conditions that have in common only the presence of skeletal muscle hyperactivity, for example, the muscle spasms that can occur in MULTIPLE SCLEROSIS. (From Smith and Reynard, Textbook of Pharmacology, 1991, p358)

A subclass of analgesic agents that typically do not bind to OPIOID RECEPTORS and are not addictive. Many non-narcotic analgesics are offered as NONPRESCRIPTION DRUGS.

76 - 88%

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

1.43 ± 0.18 L/kg [Healthy Pediatric Controls]

0.17 L/h/kg [healthy]

Following oral administration of a single 600-mg dose of quinine sulfate in healthy adults, the mean plasma clearance was 0.08-0.47 L/hour per kg (median: 0.17 L/hour per kg) and the mean plasma elimination half-life was 9.7-12.5 hours. Following oral administration of 10 mg/kg of quinine sulfate in patients with uncomplicated malaria, mean total clearance of quinine was decreased (approximately 0.09 L/hour per kg) during the acute phase of the infection and increased (approximately 0.16 L/hour per kg) during the recovery or convalescent phase.

Following oral administration of a single 600-mg dose of quinine sulfate in geriatric and younger adults, the mean clearance of the drug was decreased (0.06 versus 0.08 L/hour per kg) and the mean elimination half-life was significantly increased (18.4 versus 10.5 hours) in geriatric adults compared with younger adults. Although renal clearance of quinine was similar in geriatric and younger adults, geriatric adults excreted a larger proportion of the dose in urine as unchanged drug compared with younger adults (16.6 versus 11.2%). The steady-state pharmacokinetics after a quinine sulfate dosage of 648 mg 3 times daily for 7 days were similar in healthy geriatric adults 65-78 years of age and healthy younger adults 20-39 years of age; however, the mean elimination half-life was 24 hours in the geriatric individuals compared with 20 hours in the younger adults.

Medicine (antimalarial) as the alkaloid or as numerous salts and derivatives; flavoring in carbonated beverages

Flavor in carbonated beverages.

MEDICATION

MEDICATION (VET)

For more Uses (Complete) data for QUININE (8 total), please visit the HSDB record page.

Use (kg; approx.) in Germany (2009): >5000

(1972) No Data

(1975) No Data

(1972) 4.8X10+7 GRAMS

(1975) 4.87X10+7 GRAMS

(1972) PROBABLY GREATER THAN 4.54X10+5 GRAMS

(1975) PROBABLY GREATER THAN 4.54X10+5 GRAMS

EXTRACTION FROM CINCHONA BARK WITH SLAKED LIME, FOLLOWED BY AQ SODIUM HYDROXIDE OR CARBONATE TREATMENT, EXTRACTION INTO HOT MINERAL OIL, SEPN USING SULFURIC ACID, THEN DIL SODIUM HYDROXIDE, & PURIFICATION BY RECRYSTALLIZATION

Finely ground cinchona bark mixed with lime is extracted with hot, high-boiling paraffin oil. The solution is filtered, shaken with dilute sulfuric acid, and the latter neutralized while still hot with sodium carbonate; on cooling, quinine sulfate crystallized out. The sulfate is then treated with ammonia, the alkaloid being obtained.

Cosmetics -> Hair conditioning

Pharmaceuticals -> Animal Drugs -> Approved in Taiwan

Cinchonan-9-ol, 6'-methoxy-, (8.alpha.,9R)-: ACTIVE

Quinine is the chief alkaloid of cinchona, the powdered bark of the South American cinchona tree, otherwise known as Peruvian, Jesuit's, or Cardinal's bark.

Quinine, the first known antimalarial, is a 4-quinolinemethanol that has served as a model for the design of numerous antiplasmodial drugs. Its history began in mid-seventeenth century Peru when the Incas told the Jesuits of the medicinal properties of the bark of an evergreen mountain tree they called quina-quina (later called cinchona). The bark, when made into an aqueous infusion,was capable of curing malaria. The use of cinchona spread to Europe and the alkaloid from it, quinine, was isolated in 1820.