Quinine

324.42

324.42

91867

205-003-2

DTXSID0044280

Triboluminescent, orthorhombic needles from absolute alcohol|Bulky, white, amorphous powder or crystalline alkaloid|CRYSTALS TURN BROWN ON EXPOSURE TO AIR

29392110

45.6

log Kow = 2.88

White Crystalline Powder

1.1294 (rough estimate)

57 °C

462.75°C (rough estimate)

>110°C (>230°F)

1.6250 (estimate)

H2O: slightly soluble

Refrigerator

0mmHg at 25°C

-172 º (c=1, EtOH)

ODORLESS

Very bitter taste

Henry's Law constant = 8.58X10-16 atm-cu m/mol at 25 °C (est)

pK1 (18 °C) = 5.07; pK2 = 9.7

Sublimes in high vacuum at 170-180 °C blue fluorescence is especially strong in dilute sulfuric acid|Quinine sulfate occurs as fine, needle-like, white crystals which are usually lusterless and make a light and readily compressible mass; the drug has a persistent, very bitter taste. Quinine sulfate has solubilities of approximately 2 mg/mL in water and 8.3 mg/mL in alcohol at 25 °C. /Quinine sulfate/|Very bitter crystals or crystalline powder; efflorescent on exposure to air and darkens on exposure to light. One gram dissolves in 9 mL water, 0.7 mL boiling water, 23 mL alcohol, 0.7 mL alcohol at 60 °C, 625 mL chloroform, 2500 mL ether, 15 mL glycerol; pH: 3.5 /Bisulfate heptahydrate/|Bitter, silky needles. Effloresces on expsoure to warm air. Does not lose all its water below 120 °C. One gram dissolves in 16 mL water, in 0.5 mL boiling water, in 1.0 mL alcohol, in about 7.0 mL glycerol, in about 1 ml chloroform, in about 350 mL ether. pH (1% aqueous solution): 6.0-7.0. Bitterness threshold 1:30000 /Quinine hydrochloride dihydrate/|For more Other Experimental Properties (Complete) data for QUININE (6 total), please visit the HSDB record page.

III

6.1(b)

1544

3

36/37/38-42/43-22-20/22-20/21/22-36/38

22-26-36/37-45-37/39-36-7

VA6020000

Xn,Xi

Quinidine gluconate, quinidine polygalacturonate, and quinidine sulfate darken on exposure to light and should be stored in well-closed, light resistant containers. Solutions of quinidine salts slowly acquire a brownish tint on exposure to light. Only colorless, clear solutions of quinidine gluconate injection should be used. Quinidine gluconate injection should be stored at 15-30 °C. When diluted to a concentration of 16 mg/ml with 5% dextrose injection, quinidine gluconate injection is stable for 24 hours at room temperature and up to 48 hours when refrigerated. /Quinidine salts/

P261-P280-P284-P304 + P340-P305 + P351 + P338-P342 + P311

H315-H317-H319-H334

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.

Incompatible materials: Strong oxidizing agents.

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.

|Danger|H302 (52.91%): Harmful if swallowed [Warning Acute toxicity, oral]|P261, P264, P270, P272, P280, P285, P301+P312, P302+P352, P304+P341, P305+P351+P338, P321, P330, P332+P313, P333+P313, P337+P313, P342+P311, P362, P363, and P501|Aggregated GHS information provided by 327 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]|P261, P264, P270, P272, P280, P301+P312, P302+P352, P321, P330, P333+P313, P363, and P501|H315: Causes skin irritation [Warning Skin corrosion/irritation]|P261, P264, P272, P280, P285, P302+P352, P304+P341, P305+P351+P338, P321, P332+P313, P333+P313, P337+P313, P342+P311, P362, P363, and P501

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).

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.

Special hazards arising from the substance or mixture: Carbon oxides, nitrogen oxides (NOx).

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.

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.

Skin irritant.

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.

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.

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.

The average fatal dose for an adult is about 8 g although deaths have been reported from as little as 1.5 g in an adult and 900 mg in a child.|A lethal dose of quinine has not been clearly defined, but fatalities have been reported after the ingestion of 2 to 8 grams in adults.

LD50 Guinea pig oral 1800 mg/kg|LD50 Mouse ip 115 mg/kg

In patients with severe hepatic impairment (Child-Pugh C), quinine oral clearance (CL/F) is decreased, volume of distribution (Vd/F) is increased, and half-life is prolonged, relative to subjects with normal liver function. Therefore, quinine is not indicated in patients with severe hepatic impairment and alternate therapy should be administered.|Quinine should be used with caution in patients with atrial fibrillation or atrial flutter. A paradoxical increase in ventricular response rate may occur with quinine, similar to that observed with quinidine.|Quinine is contraindicated in patients with G-6-PD deficiency, myasthenia gravis, or optic neuritis.|Quinine is contraindicated in patients with prolonged QT interval.The drug should be avoided in patients with clinical conditions known to prolong the QT interval (e.g., uncorrected hypokalemia, bradycardia, certain cardiac conditions).|For more Populations at Special Risk (Complete) data for QUININE (6 total), please visit the HSDB record page.

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.

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.

QUININE CAUSED ALLERGIC CONTACT DERMATITIS IN EXPOSED WORKERS. PATCH TESTING WAS PERFORMED. SAFETY MEASURES FOR PREVENTION OF DERMATITIS ARE DISCUSSED.|Chronic exposure to quinine occurs in those who take it medically, and in heroin addicts who use quinine adulterated drug.

Quinine is a natural cinchona alkaloid that has been used for centuries in the prevention and therapy of malaria. Quinine is also used for idiopathic muscle cramps. Quinine therapy has been associated with rare instances of hypersensitivity reactions which can be accompanied by hepatitis and mild jaundice.

Antimalarial Agents

Analgesics, Non-Narcotic; Antimalarials; Muscle Relaxants, Central|Qualaquin (quinine sulfate) is an antimalarial drug indicated only for treatment of uncomplicated Plasmodium falciparum malaria. Quinine sulfate has been shown to be effective in geographical regions where resistance to chloroquine has been documented. /Included in US product label/|Oral quinine sulfate is used in conjunction with IV or oral clindamycin for the treatment of babesiosis caused by Babesia microti. /NOT included in US product label/|Although quinine sulfate is not approved by the FDA for the treatment of severe or complicated malaria, the CDC states that oral quinine sulfate can be used in conjunction with doxycycline, tetracycline, or clindamycin for follow-up treatment after an appropriate initial parenteral regimen.|For more Therapeutic Uses (Complete) data for QUININE (8 total), please visit the HSDB record page.

/BOXED WARNING/ WARNING: Qualaquin use for the treatment or prevention of nocturnal leg cramps may result in serious and life-threatening hematologic reactions, including thrombocytopenia and hemolytic uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP). Chronic renal impairment associated with the development of TTP has been reported. The risk associated with Qualaquin use in the absence of evidence of its effectiveness in the treatment or prevention of nocturnal leg cramps outweighs any potential benefit.|Serious hypersensitivity reactions, including anaphylactic shock, anaphylactoid reactions, urticaria, serious skin rashes (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis), 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.|Serious, life-threatening, and sometimes fatal hematologic reactions, including thrombocytopenia and thrombocytopenia, hemolytic uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP), have been reported in patients receiving quinine, especially patients using the drug for unlabeled indications (prevention or treatment of leg cramps or restless leg syndrome). Subsequent development of chronic renal impairment has occurred in patients with quinine-associated TTP.|For more Drug Warnings (Complete) data for QUININE (37 total), please visit the HSDB record page.

The average fatal dose for an adult is about 8 g although deaths have been reported from as little as 1.5 g in an adult and 900 mg in a child.|A lethal dose of quinine has not been clearly defined, but fatalities have been reported after the ingestion of 2 to 8 grams in adults.

In combination with antibiotics, quinine is recommended as the second-line treatment for uncomplicated malaria, an alternative first-line treatment for severe malaria, and for treatment of malaria in the first trimester of pregnancy. Quinine has been shown to have frequent clinical failures, and yet the mechanisms of action and resistance have not been fully elucidated. However, resistance is linked to polymorphisms in multiple genes, including multidrug resistance 1 (Pfmdr1), the chloroquine resistance transporter (Pfcrt), and the sodium/hydrogen exchanger gene (Pfnhe1). Here, we investigated the association between in vitro quinine susceptibility and genetic polymorphisms in Pfmdr1codons 86 and 184, Pfcrt codon 76, and Pfnhe1 ms4760 in 88 field isolates from western Kenya. In vitro activity was assessed based on the drug concentration that inhibited 50% of parasite growth (the IC50), and parasite genetic polymorphisms were determined from DNA sequencing. Data revealed there were significant associations between polymorphism in Pfmdr1-86Y, Pfmdr1-184F, or Pfcrt-76T and quinine susceptibility (P < 0.0001 for all three associations). Eighty-two percent of parasites resistant to quinine carried mutant alleles at these codons (Pfmdr1-86Y, Pfmdr1-184F, and Pfcrt-76T), whereas 74% of parasites susceptible to quinine carried the wild-type allele (Pfmdr1-N86, Pfmdr1-Y184, and Pfcrt-K76, respectively). In addition, quinine IC50 values for parasites with Pfnhe1 ms4760 3 DNNND repeats were significantly higher than for those with 1 or 2 repeats (P = 0.033 and P = 0.0043, respectively). Clinical efficacy studies are now required to confirm the validity of these markers and the importance of parasite genetic background.

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.|Following oral administration of a single dose of 10 mg/kg of quinine sulfate in healthy children or pediatric patients 1.5-12 years of age with uncomplicated Plasmodium falciparum malaria, the mean total clearance (0.06 versus 0.3 L/hour per kg) is reduced and the plasma elimination half-life increased (12.1 versus 3.21 hours) in pediatric patients with malaria as compared to that observed in healthy children.|In 15 patients with uncomplicated malaria who received a 10 mg/kg oral dose of quinine sulfate, the mean total clearance of quinine was slower (approximately 0.09 L/hr/kg) during the acute phase of the infection, and faster (approximately 0.16 L/hr/kg) during the recovery or convalescent phase.|For more Absorption, Distribution and Excretion (Complete) data for QUININE (19 total), please visit the HSDB record page.

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.

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.

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

Emergency and supportive measures. 1. Maintain an open airway and assist ventilation if necessary. 2. Treat coma, seizures, hypotension, and arrhythmias if they occur. 3. Avoid types 1a and 1c antiarrhythmic drugs; they may worsen cardiotoxicity. 4. Continuously monitor vital signs and the ECG for at least 6 hours after ingestion, and admit symptomatic patients to an intensive care unit.|Specific drugs and antidotes. 1. Treat cardiotoxicity with sodium bicarbonate, ... by rapid IV bolus. 2. Stellate ganglion block has previously been recommended for quinine-induced blindness, the rationale being to increase retinal blood flow. However, recently evidence indicates that this treatment is not effective, and the procedure may have serious complications.|Decontamination. Administer activated charcoal orally if conditions are appropriate. Gastric lavage is not necessary after small to moderate ingestions if activated charcoal can be given promptly.|Enhanced elimination. Because of extensive tissue distribution (volume of distribution is 3 L/kg, dialysis and hemoperfusion procedures are ineffective. Acidification of the urine may slightly increase renal excretion but does not significantly alter the overall elimination rate and may aggravate cardiotoxicity.|For more Antidote and Emergency Treatment (Complete) data for QUININE (8 total), please visit the HSDB record page.

/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.

Table: Quinine Sulfate Preparations [Table#3926]

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.

Determination of quinine in drugs using spectrophotometric method.|Liquid chromatography determination in soft drinks.

BLOOD, FLUOROMETRY @ 365/440, BLOOD, URINE, TLC.|BLOOD, FLUOROMETRY @ 365/460.|QUININE OR QUINIDINE DETECTION IN URINE BY FLUORESCENCE ANALYSIS TLC.|QUINIDINE DETECTION IN PLASMA OR URINE BY UV SPECTROPHOTOMETRY WITH THIN LAYER CHROMATOGRAPHY CONFIRMATION.

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