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• W2045496629 endingPage "3812" @default.
• W2045496629 startingPage "3805" @default.
• W2045496629 abstract "Chloroquine accumulation by human erythrocytes infected with nine different strains of the malarial parasite Plasmodium falciparum, which varied by ⩾ 20-fold sensitivity to the drug, was measured as a function of time and drug concentration. Although the kinetics of uptake were clearly quite complex in this system, at least two general phases were observed, an extremely rapid short phase (< 30 sec), followed by a slower phase leading to steady state within 60 min. The concentration of chloroquine in the parasite food vacuole quickly exceeded 1 mM at 10−6 M external drug concentration. Minor alkalinization of this organelle was observed during the first 30 sec; this pH was reduced progressively over time in a concentration-dependent manner. The rate of pH reduction was highest in the drug-sensitive strains. Neither the rate of chloroquine accumulation nor intracellular chloroquine concentrations at steady state could adequately differentiate sensitive from resistant strains. Higher intracellular drug concentrations were required to kill resistant versus sensitive strains, suggesting that a change in sensitivity to chloroquine of an intracellular effector is the mechanism of resistance. The rapid rate and extensive accumulation of chloroquine, and the lack of significant alkalinization, indicate that a new theory of the mechanism of antimalarial action of the drug is required." @default.
• W2045496629 created "2016-06-24" @default.
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• W2045496629 date "1986-11-01" @default.
• W2045496629 modified "2023-09-25" @default.
• W2045496629 title "Uptake of [3H]chloroquine by drug-sensitive and -resistant strains of the human malaria parasite Plasmodium falciparum" @default.
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• W2045496629 doi "https://doi.org/10.1016/0006-2952(86)90668-4" @default.
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• W2045496629 hasPublicationYear "1986" @default.
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