Journal ArticleDOI
Pharmacokinetics of quinine, chloroquine and amodiaquine. Clinical implications.
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TLDR
Distribution rather than elimination processes determine the blood concentration profile of chloroquine in patients with acute malaria.Abstract:
Malaria is associated with a reduction in the systemic clearance and apparent volume of distribution of the cinchona alkaloids; this reduction is proportional to the disease severity. There is increased plasma protein binding, predominantly to alpha 1-acid glycoprotein, and elimination half-lives (in healthy adults quinine t1/2z = 11 hours, quinidine t1/2z = 8 hours) are prolonged by 50%. Systemic clearance is predominantly by hepatic biotransformation to more polar metabolites (quinine 80%, quinidine 65%) and the remaining drug is eliminated unchanged by the kidney. Quinine is well absorbed by mouth or following intramuscular injection even in severe cases of malaria (estimated bioavailability more than 85%). Quinine and chloroquine may cause potentially lethal hypotension if given by intravenous injection. Chloroquine is extensively distributed with an enormous total apparent volume of distribution (Vd) more than 100 L/kg, and a terminal elimination half-life of 1 to 2 months. As a consequence, distribution rather than elimination processes determine the blood concentration profile of chloroquine in patients with acute malaria. Parenteral chloroquine should be given either by continuous intravenous infusion, or by frequent intramuscular or subcutaneous injections of relatively small doses. Oral bioavailability exceeds 75%. Amodiaquine is a pro-drug for the active antimalarial metabolite desethylamodiaquine. Its pharmacokinetic properties are similar to these of chloroquine although the Vd is smaller (17 to 34 L/kg) and the terminal elimination half-life is 1 to 3 weeks.read more
Citations
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Summary of product characteristics
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Classification of orally administered drugs on the World Health Organization Model list of Essential Medicines according to the biopharmaceutics classification system.
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Use of In Vitro and In Vivo Data to Estimate the Likelihood of Metabolic Pharmacokinetic Interactions
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WHO Guidelines for the treatment of malaria
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Severe falciparum malaria in children: current understanding of pathophysiology and supportive treatment.
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References
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Journal ArticleDOI
TNF concentration in fatal cerebral, non-fatal cerebral, and uncomplicated Plasmodium falciparum malaria.
Dominic P. Kwiatkowski,Adrian V. S. Hill,I. Sambou,P. Twumasi,J. Castracane,K. R. Manogue,Anthony Cerami,David Brewster,Brian Greenwood +8 more
TL;DR: It is concluded that increased TNF production is a normal host response to P falciparum infection, but that excessive levels of production may predispose to cerebral malaria and a fatal outcome.
Journal ArticleDOI
Inhibition by chloroquine of a novel haem polymerase enzyme activity in malaria trophozoites.
A. F. G. Slater,A. Cerami +1 more
TL;DR: The identification and characterization of a haem polymerase enzyme activity from extracts of Plasmodium fal-ciparum trophozoites are reported and show that this enzyme is inhibited by quinoline-containing drugs such as chloroquine and quinine, providing a possible explanation for the highly stage-specific anti-malarial properties of these drugs.
Book
Chemotherapy and drug resistance in malaria
TL;DR: Chemotherapy and drug resistance in malaria as discussed by the authors, Chemotherapy and Drug Resistance in malaria, کتابخانه مرکزی دانشگاه علوم پزش
Journal ArticleDOI
Plasmodium vivax resistance to chloroquine
TL;DR: Two soldiers continued weekly prophylaxis with 300 mg chloroquine base on their return to Australia from Papua New Guinea but were not protected against Plasmodium vivax malaria, suggesting the emergence of strains of P v Vivax with a reduced susceptibility to chloroquines.
Journal ArticleDOI
The epidemiology of drug-resistant malaria.
TL;DR: This article will focus on resistance occurring in chemotherapy rather than prophylaxis, and host factors, including pharmacokinetics and immunity, will not be reviewed.
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