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- W2024930127 abstract "The kinetics of uptake of chloroquine into isolated rat hepatocytes were studied to further investigate whether they are consistent with accumulation of chloroquine at therapeutic concentrations that is predominantly due to lysosomal trapping. A mathematical model describing the disposition of weak bases in isolated hepatocytes was developed and fitted to the chloroquine uptake data, allowing estimation of permeability coefficients for un-ionized chloroquine transport across rate-limiting membranes (p0 = 5.9 +/- 0.5 cm. s-1). The results of these studies suggest that the lysosomal membrane is the rate-limiting membrane in uptake of chloroquine in isolated hepatocytes. The rate and extent of accumulation of chloroquine in isolated hepatocytes in the presence of 10 mM NH4Cl were decreased. These results are consistent with a reduction in lysosomal pH caused by NH4Cl. The kinetics of uptake of hydroxychloroquine, which is structurally similar to chloroquine, were also investigated. The results of these studies were also consistent with lysosomal trapping, although the p0 value for un-ionized hydroxychloroquine (p0 = 0.28 +/- 0.02 cm.s-1) was much lower than that for un-ionized chloroquine. The estimated p0 value for un-ionized chloroquine and hydroxychloroquine transport across the lysosomal membrane are of a similar magnitude to those reported for transport of these compounds across human erythrocyte membranes, suggesting a similar transport mechanism." @default.
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- W2024930127 title "Kinetics of Chloroquine Uptake into Isolated Rat Hepatocytes" @default.
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- W2024930127 doi "https://doi.org/10.1002/jps.2600820610" @default.
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