ArticleThe Journal of pharmacology and experimental therapeutics2011
Effect of phospholipidosis on the cellular pharmacokinetics of chloroquine.
Article in The Journal of pharmacology and experimental therapeutics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 56 citations in OpenAlex.
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- Quantitative Raman chemical imaging of intracellular drug-membrane aggregates and small molecule drug precipitates in cytoplasmic organelles.Advanced drug delivery reviews · 2023Review
- Utility of Minimal Physiologically Based Pharmacokinetic Models for Assessing Fractional Distribution, Oral Absorption, and Series-Compartment Models of Hepatic Clearance.Drug metabolism and disposition: the biological fate of chemicals · 2023Article
- Osmotically Rupturing Phagosomes in Macrophages Using PNIPAM Microparticles.ACS applied materials & interfaces · 2023Article
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- Molecular design of a pathogen activated, self-assembling mechanopharmaceutical device.Journal of controlled release : official journal of the Controlled Release Society · 2022Review
- Repurposing Quinoline and Artemisinin Antimalarials as Therapeutics for SARS-CoV-2: Rationale and Implications.ACS pharmacology & translational science · 2021Review
- Physiologically Based Pharmacokinetics of Lysosomotropic Chloroquine in Rat and Human.The Journal of pharmacology and experimental therapeutics · 2021Article
- Consideration of the Unbound Drug Concentration in Enzyme Kinetics.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Review
- An Experimental Model for Peri-conceptual COVID-19 Pregnancy Loss and Proposed Interventions to Optimize Outcomes.International journal of molecular and cellular medicine · 2020Review
- Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro.Cell discovery · 2020Article
- Biogenesis of lysosome-related organelles complex-1 (BORC) regulates late endosomal/lysosomal size through PIKfyve-dependent phosphatidylinositol-3,5-bisphosphate.Traffic (Copenhagen, Denmark) · 2019Article
- Review
- An Expandable Mechanopharmaceutical Device (3): a Versatile Raman Spectral Cytometry Approach to Study the Drug Cargo Capacity of Individual Macrophages.Pharmaceutical research · 2018Article
- New insights into the intracellular distribution pattern of cationic amphiphilic drugs.Scientific reports · 2017Article
- The secretion and biological function of tumor suppressor maspin as an exosome cargo protein.Oncotarget · 2017Article
- Predicting volume of distribution with decision tree-based regression methods using predicted tissue:plasma partition coefficients.Journal of cheminformatics · 2015Article
- Imaging the intracellular distribution of tyrosine kinase inhibitors in living cells with quantitative hyperspectral stimulated Raman scattering.Nature chemistry · 2014Article
- Identification of hepatic phospholipidosis inducers in sandwich-cultured rat hepatocytes, a physiologically relevant model, reveals altered basolateral uptake and biliary excretion of anionic probe substrates.Toxicological sciences : an official journal of the Society of Toxicology · 2014Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
In vivo, the weakly basic, lipophilic drug chloroquine (CQ) accumulates in the kidney to concentrations more than a thousand-fold greater than those in plasma. To study the cellular pharmacokinetics of chloroquine in cells derived from the distal tubule, Madin-Darby canine kidney cells were incubated with CQ under various conditions. CQ progressively accumulated without exhibiting steady-state behavior. Experiments failed to yield evidence that known active transport mechanisms mediated CQ uptake at the plasma membrane. CQ induced a phospholipidosis-like phenotype, characterized by the appearance of numerous multivesicular and multilamellar bodies (MLBs/MVBs) within the lumen of expanded cytoplasmic vesicles. Other induced phenotypic changes including changes in the volume and pH of acidic organelles were measured, and the integrated effects of all these changes were computationally modeled to establish their impact on intracellular CQ mass accumulation. Based on the passive transport behavior of CQ, the measured phenotypic changes fully accounted for the continuous, nonsteady-state CQ accumulation kinetics. Consistent with the simulation results, Raman confocal microscopy of live cells confirmed that CQ became highly concentrated within induced, expanded cytoplasmic vesicles that contained multiple MLBs/MVBs. Progressive CQ accumulation was increased by sucrose, a compound that stimulated the phospholipidosis-like phenotype, and was decreased by bafilomycin A1, a compound that inhibited this phenotype. Thus, phospholipidosis-associated changes in organelle structure and intracellular membrane content can exert a major influence on the local bioaccumulation and biodistribution of drugs.
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Registered trials
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