Antimalarial 4‐aminoquinolines: mode of action and pharmacokinetics
Identifieur interne : 002D02 ( Main/Exploration ); précédent : 002D01; suivant : 002D03Antimalarial 4‐aminoquinolines: mode of action and pharmacokinetics
Auteurs : E. Pussard [France] ; F. Verdier [France]Source :
- Fundamental & Clinical Pharmacology [ 0767-3981 ] ; 1994-01-02.
English descriptors
- Teeft :
- Aderounmu, Amodiaquine, Amopyroquine, Antimalarial, Antimalarial activity, Antimicrob, Antimicrob agents chemother, Blood cells, Blood pressure, Bra, Calcium channel blockers, Chemother, Chemotherapy, Chloroquine, Chloroquine resistance, Chloroquine treatment, Clavier, Clin, Clin pharmacol, Desethylchloroquine, Dos, Drug resistance, Erythrocyte, Falciparum, Falciparum malaria, Ferriprotoporphyrin, Gustafsson, Healthy subjects, Healthy volunteers, Intramuscular, Intramuscular chloroquine, Intramuscular injection, Intravenous, Intravenous administration, Kinetics, Kwashiorkor, Lancet, Malaria, Malaria patients, Monodesethylamodiaquine, Monodesethylchloroquine, Oral administration, Oral dose, Parasite, Parenteral, Peak plasma concentration, Pharmacokinetic, Pharmacokinetics, Pharmacol, Plasma concentrations, Plasmodium, Plasmodium falciparum, Plasmodium falciparum malaria, Polymerase, Prophylaxis, Protein binding, Pussard, Regimen, Resistant parasites, Salako, Severe malaria, Therapeutic regimen, Therapeutic regimens, Toxicity, Unpublished data, Urine, Verdier, Winstanley.
Abstract
Summary— In the last ten years, the widespread increase in Plasmodium falciparum resistance to chloroquine has prompted research into antimalarial 4‐aminoquinolines, empirically used up to now. The mechanism of action of 4‐aminoquinolines is characterized by the concentration of the drug in the digestive vacuole of the intraerythrocytic parasite. Various hypotheses have been advanced to explain the specificity of action on the parasite; the most recent one is the inhibition of the haem polymerase of the parasite, leading to the accumulation of soluble haem toxic for the parasite. Chloroquine‐resistant parasites accumulate the drug to a lesser extent than do sensitive parasites. Recent findings have shown that chloroquine resistance can be reversed by various tricyclic drugs, which are able to restore the effective concentrations of chloroquine in the infected erythrocyte, but intrinsic mechanisms of action of these reversing agents are unknown. Four‐aminoquinolines are extensively distributed in tissues and characterized by a long elimination half‐life. Despite similarities in their chemical structures, these drugs show differences in their biotransformation and routes of elimination: chloroquine is partly metabolized into a monodesethylderivative and eliminated mainly by the kidney. In contrast, amodiaquine is a prodrug and amopyroquine is poorly metabolized; both drugs are excreted mainly in the bile. The understanding of the pharmacokinetics of 4‐aminoquinolines has led to an improvement in empirically defined therapeutic regimens. Finally, the emergence of severe adverse‐effects after prolonged prophylaxis with amodiaquine and the lack of cross resistance of Plasmodium falciparum between chloroquine and amopyroquine, have led to a proposal for the use of intramuscular amopyroquine as an alternative for the treatment of chloroquine‐resistant malaria.
Url:
DOI: 10.1111/j.1472-8206.1994.tb00774.x
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream Istex, to step Corpus: 000283
- to stream Istex, to step Curation: 000283
- to stream Istex, to step Checkpoint: 001A87
- to stream Main, to step Merge: 002D62
- to stream Main, to step Curation: 002D02
Le document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Antimalarial 4‐aminoquinolines: mode of action and pharmacokinetics</title><author><name sortKey="Pussard, E" sort="Pussard, E" uniqKey="Pussard E" first="E." last="Pussard">E. Pussard</name></author><author><name sortKey="Verdier, F" sort="Verdier, F" uniqKey="Verdier F" first="F." last="Verdier">F. Verdier</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:BA2F28BB305766583597CBFD4AB779430D57C916</idno><date when="1994" year="1994">1994</date><idno type="doi">10.1111/j.1472-8206.1994.tb00774.x</idno><idno type="url">https://api.istex.fr/ark:/67375/WNG-PLB9MK8X-6/fulltext.pdf</idno><idno type="wicri:Area/Istex/Corpus">000283</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">000283</idno><idno type="wicri:Area/Istex/Curation">000283</idno><idno type="wicri:Area/Istex/Checkpoint">001A87</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Checkpoint">001A87</idno><idno type="wicri:doubleKey">0767-3981:1994:Pussard E:antimalarial:aminoquinolines:mode</idno><idno type="wicri:Area/Main/Merge">002D62</idno><idno type="wicri:Area/Main/Curation">002D02</idno><idno type="wicri:Area/Main/Exploration">002D02</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main">Antimalarial 4‐aminoquinolines: mode of action and pharmacokinetics</title><author><name sortKey="Pussard, E" sort="Pussard, E" uniqKey="Pussard E" first="E." last="Pussard">E. Pussard</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Service de Pharmacologie Clinique, Hôpital de Bicêlre, 78, avenue du Général Leclerc, 94275 Le Kremlin Bicêtre Cedex</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Le Kremlin Bicêtre</settlement></placeName></affiliation><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>INSERM Unité 13, Hôpital Claude Bernard, 190, boulevard Mac Donald, 75944 Paris Cedex 19</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Verdier, F" sort="Verdier, F" uniqKey="Verdier F" first="F." last="Verdier">F. Verdier</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>INSERM Unité 13, Hôpital Claude Bernard, 190, boulevard Mac Donald, 75944 Paris Cedex 19</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Fundamental & Clinical Pharmacology</title><title level="j" type="alt">FUNDAMENTAL CLINICAL PHARMACOLOGY</title><idno type="ISSN">0767-3981</idno><idno type="eISSN">1472-8206</idno><imprint><biblScope unit="vol">8</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="1">1</biblScope><biblScope unit="page" to="17">17</biblScope><biblScope unit="page-count">17</biblScope><publisher>Blackwell Publishing Ltd</publisher><pubPlace>Oxford, UK</pubPlace><date type="published" when="1994-01-02">1994-01-02</date></imprint><idno type="ISSN">0767-3981</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0767-3981</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="Teeft" xml:lang="en"><term>Aderounmu</term><term>Amodiaquine</term><term>Amopyroquine</term><term>Antimalarial</term><term>Antimalarial activity</term><term>Antimicrob</term><term>Antimicrob agents chemother</term><term>Blood cells</term><term>Blood pressure</term><term>Bra</term><term>Calcium channel blockers</term><term>Chemother</term><term>Chemotherapy</term><term>Chloroquine</term><term>Chloroquine resistance</term><term>Chloroquine treatment</term><term>Clavier</term><term>Clin</term><term>Clin pharmacol</term><term>Desethylchloroquine</term><term>Dos</term><term>Drug resistance</term><term>Erythrocyte</term><term>Falciparum</term><term>Falciparum malaria</term><term>Ferriprotoporphyrin</term><term>Gustafsson</term><term>Healthy subjects</term><term>Healthy volunteers</term><term>Intramuscular</term><term>Intramuscular chloroquine</term><term>Intramuscular injection</term><term>Intravenous</term><term>Intravenous administration</term><term>Kinetics</term><term>Kwashiorkor</term><term>Lancet</term><term>Malaria</term><term>Malaria patients</term><term>Monodesethylamodiaquine</term><term>Monodesethylchloroquine</term><term>Oral administration</term><term>Oral dose</term><term>Parasite</term><term>Parenteral</term><term>Peak plasma concentration</term><term>Pharmacokinetic</term><term>Pharmacokinetics</term><term>Pharmacol</term><term>Plasma concentrations</term><term>Plasmodium</term><term>Plasmodium falciparum</term><term>Plasmodium falciparum malaria</term><term>Polymerase</term><term>Prophylaxis</term><term>Protein binding</term><term>Pussard</term><term>Regimen</term><term>Resistant parasites</term><term>Salako</term><term>Severe malaria</term><term>Therapeutic regimen</term><term>Therapeutic regimens</term><term>Toxicity</term><term>Unpublished data</term><term>Urine</term><term>Verdier</term><term>Winstanley</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Summary— In the last ten years, the widespread increase in Plasmodium falciparum resistance to chloroquine has prompted research into antimalarial 4‐aminoquinolines, empirically used up to now. The mechanism of action of 4‐aminoquinolines is characterized by the concentration of the drug in the digestive vacuole of the intraerythrocytic parasite. Various hypotheses have been advanced to explain the specificity of action on the parasite; the most recent one is the inhibition of the haem polymerase of the parasite, leading to the accumulation of soluble haem toxic for the parasite. Chloroquine‐resistant parasites accumulate the drug to a lesser extent than do sensitive parasites. Recent findings have shown that chloroquine resistance can be reversed by various tricyclic drugs, which are able to restore the effective concentrations of chloroquine in the infected erythrocyte, but intrinsic mechanisms of action of these reversing agents are unknown. Four‐aminoquinolines are extensively distributed in tissues and characterized by a long elimination half‐life. Despite similarities in their chemical structures, these drugs show differences in their biotransformation and routes of elimination: chloroquine is partly metabolized into a monodesethylderivative and eliminated mainly by the kidney. In contrast, amodiaquine is a prodrug and amopyroquine is poorly metabolized; both drugs are excreted mainly in the bile. The understanding of the pharmacokinetics of 4‐aminoquinolines has led to an improvement in empirically defined therapeutic regimens. Finally, the emergence of severe adverse‐effects after prolonged prophylaxis with amodiaquine and the lack of cross resistance of Plasmodium falciparum between chloroquine and amopyroquine, have led to a proposal for the use of intramuscular amopyroquine as an alternative for the treatment of chloroquine‐resistant malaria.</div></front></TEI><affiliations><list><country><li>France</li></country><region><li>Île-de-France</li></region><settlement><li>Le Kremlin Bicêtre</li><li>Paris</li></settlement></list><tree><country name="France"><region name="Île-de-France"><name sortKey="Pussard, E" sort="Pussard, E" uniqKey="Pussard E" first="E." last="Pussard">E. Pussard</name></region><name sortKey="Pussard, E" sort="Pussard, E" uniqKey="Pussard E" first="E." last="Pussard">E. Pussard</name><name sortKey="Verdier, F" sort="Verdier, F" uniqKey="Verdier F" first="F." last="Verdier">F. Verdier</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/ChloroquineV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 002D02 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 002D02 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= ChloroquineV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= ISTEX:BA2F28BB305766583597CBFD4AB779430D57C916
|texte= Antimalarial 4‐aminoquinolines: mode of action and pharmacokinetics
}}
| This area was generated with Dilib version V0.6.33. |  |