ArticleMalaria journal2014
Atovaquone and quinine anti-malarials inhibit ATP binding cassette transporter activity.
Article in Malaria journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- Pooled it
- Unanticipated CNS Safety Signal in a Placebo-Controlled, Randomized Trial of Co-Administered Atovaquone-Proguanil and Amodiaquine.Clinical pharmacology and therapeutics · 2022Trial
- Selective Inhibition of the ABCG2 Transporter by Primaquine Derivatives Reverses the Multidrug Resistance of Tumor Cells.International journal of molecular sciences · 2025Article
- Exploring Quinoline Derivatives: Their Antimalarial Efficacy and Structural Features.Medicinal chemistry (Shariqah (United Arab Emirates)) · 2025Review
- Crushing lopinavir/ritonavir tablets does not result in lower exposure to lopinavir/ritonavir in adult patients with COVID-19.European journal of hospital pharmacy : science and practice · 2023Article
- A curated binary pattern multitarget dataset of focused ATP-binding cassette transporter inhibitors.Scientific data · 2022Article
- Methodology to streamline flow cytometric-based detection of early stage Plasmodium parasitemia in mice.Journal of microbiological methods · 2022Article
- ADME and Pharmacokinetic Properties of Remdesivir: Its Drug Interaction Potential.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Extracellular Vesicles as Mediators of Cancer Disease and as Nanosystems in Theranostic Applications.Cancers · 2021Review
- Synthesis and biological evaluation of novel quinoline analogs of ketoprofen as multidrug resistance protein 2 (MRP2) inhibitors.Iranian journal of basic medical sciences · 2021Article
- Repositioning of Antiparasitic Drugs for Tumor Treatment.Frontiers in oncology · 2021Review
- Intracellular ABCB1 as a Possible Mechanism to Explain the Synergistic Effect of Hydroxychloroquine-Azithromycin Combination in COVID-19 Therapy.The AAPS journal · 2020Article
- Metabolism and Interactions of Chloroquine and Hydroxychloroquine with Human Cytochrome P450 Enzymes and Drug Transporters.Current drug metabolism · 2020Review
- Dihydroartemisinin Sensitizes Mutant p53 (R248Q)-Expressing Hepatocellular Carcinoma Cells to Doxorubicin by Inhibiting P-gp Expression.BioMed research international · 2019Article
- Biologically active quinoline and quinazoline alkaloids part II.Medicinal research reviews · 2018Review
- Atovaquone Impairs Growth of Aspergillus and Fusarium Keratitis Isolates by Modulating Mitochondrial Function and Zinc Homeostasis.Investigative ophthalmology & visual science · 2018Article
- Transcriptome analysis of genes associated with breast cancer cell motility in response to Artemisinin treatment.BMC cancer · 2017Article
- Article
- Proguanil and cycloguanil are organic cation transporter and multidrug and toxin extrusion substrates.Malaria journal · 2017Article
- Downregulation of Organic Anion Transporting Polypeptide (OATP) 1B1 Transport Function by Lysosomotropic Drug Chloroquine: Implication in OATP-Mediated Drug-Drug Interactions.Molecular pharmaceutics · 2016Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTherapeutic blood plasma concentrations of anti-malarial drugs are essential for successful treatment. Pharmacokinetics of pharmaceutical compounds are dependent of adsorption, distribution, metabolism, and excretion. ATP binding cassette (ABC) transport proteins are particularly involved in drug deposition, as they are located at membranes of many uptake and excretory organs and at protective barriers, where they export endogenous and xenobiotic compounds, including pharmaceuticals. In this study, a panel of well-established anti-malarial drugs which may affect drug plasma concentrations was tested for interactions with human ABC transport proteins.
methodsThe interaction of chloroquine, quinine, artemisinin, mefloquine, lumefantrine, atovaquone, dihydroartemisinin and proguanil, with transport activity of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), bile salt export pump (BSEP) and multidrug resistance-associated proteins (MRP) 1-4 were analysed. The effect of the anti-malarials on the ATP-dependent uptake of radio-labelled substrates was measured in membrane vesicles isolated from HEK293 cells overexpressing the ABC transport proteins.
resultsA strong and previously undescribed inhibition of BCRP-mediated transport by atovaquone with a 50% inhibitory concentration (IC50) of 0.23 μM (95% CI 0.17-0.29 μM) and inhibition of P-gp-mediated transport by quinine with an IC50 of 6.8 μM (95% CI 5.9-7.8 μM) was observed. Furthermore, chloroquine and mefloquine were found to significantly inhibit P-gp-mediated transport. BCRP transport activity was significantly inhibited by all anti-malarials tested, whereas BSEP-mediated transport was not inhibited by any of the compounds. Both MRP1- and MRP3-mediated transport were significantly inhibited by mefloquine.
conclusionsAtovaquone and quinine significantly inhibit BCRP- and P-gp- mediated transport at concentrations within the clinically relevant prophylactic and therapeutic range. Co-administration of these established anti-malarials with drugs that are BCRP or P-gp substrates may potentially lead to drug-drug interactions.
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Registered trials
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