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.
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.
来源:Hazardous Substances Data Bank (HSDB)
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奎宁是P-糖蛋白的底物，也是其抑制剂，有可能影响那些是P-糖蛋白底物的药物的转运。
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.
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.
Enantioselective synthesis of chiral 4 H -pyran derivatives through [3+3] tandem reaction over a squaramide catalyst
摘要：
An efficient [3+3] tandem reaction between 1-phenyl-3-methyl-5-pyrazolones and 2-(1-alkynyl)-2alken-1-ones over a tertiary amine-squaramide catalyst is described. The pyran fused pyrazolone derivatives were successfully obtained in 53-88% yields and with 62-84% ee by this synthetic methodology. This methodology involves easily accessible starting material, mild condition, satisfied yields and ee values. Additionally, when enynes were used as the substrates for the [3+3] cascade reaction, isomerized target products could be obtained directly. (C) 2017 Elsevier Ltd. All rights reserved.
Reaction of alcohols and amines with diacetyldihydrofluorescein (DADF): Conversion into erythrosine-derivatives on TLC-plates by ammonia and iodine vapors
作者：Paam N. Sharma、Arnold Brossi
DOI：10.1002/hlca.19840670136
日期：1984.2.1
Reaction of decetylcolchicine (2) and colchifoline (3) with diacetyldihydrofluorescein (1, DADF) afforded the corresponding amide and ester derivatives, converted on TLC-plates after exposure to ammonia and iodinevapors into red colored pigments. This reaction, also observed with DADF-derivatives of codeine, quinine and mescaline is highly sensitive. The red pigment produced from the DADF-ester (6)
METHOD FOR THE PRODUCTION OF 1,4-BENZOTHIEPIN-1,1-DIOXIDE DERIVATIVES
申请人：Billen Guenter
公开号：US20110245486A1
公开（公告）日：2011-10-06
The invention relates to a method for producing 1,4-benzothiepin-1,1-dioxide derivatives substituted with benzyl groups.
这项发明涉及一种生产取代苯甲基基团的1,4-苯并噻吩-1,1-二氧化物衍生物的方法。
Synthesis and characterization of chiral ionic liquids based on quinine, l-proline and l-valine for enantiomeric recognition
作者：Tânia E. Sintra、Mikhail G. Gantman、Sónia P.M. Ventura、João A.P. Coutinho、Peter Wasserscheid、Peter S. Schulz
DOI：10.1016/j.molliq.2019.03.084
日期：2019.6
separation of enantiomers remains a major challenge for the pharmaceutical industry. In this work, eight chiralionicliquids (CILs) directly derived from the ‘chiral pool’ were synthesized and characterized in order to develop enantioselective systems, for the chiral resolution. According to their chiral cations, three different groups of CILs were prepared, namely based on quinine, l-proline and l-valine
Organocatalytic Asymmetric Peroxidation of γ,δ-Unsaturated β-Keto Esters—A Novel Route to Chiral Cycloperoxides
作者：Mary C. Hennessy、Hirenkumar Gandhi、Timothy P. O’Sullivan
DOI：10.3390/molecules28114317
日期：——
A methodology for the asymmetric peroxidation of γ,δ-unsaturated β-ketoesters is presented. Using a cinchona-derived organocatalyst, the target δ-peroxy-β-keto esters were obtained in high enantiomeric ratios of up to 95:5. Additionally, these δ-peroxy esters can be readily reduced to chiral δ-hydroxy-β-keto esters without impacting the β-ketoester functionality. Importantly, this chemistry opens
