ArticleMalaria journal2017
Proguanil and cycloguanil are organic cation transporter and multidrug and toxin extrusion substrates.
Article in Malaria journal, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 22 citations in OpenAlex.
- Effects of proton pump inhibitors, esomeprazole and vonoprazan, on the disposition of proguanil, a CYP2C19 substrate, in healthy volunteers.British journal of clinical pharmacology · 2019Trial
- Structure-Guided Identification of Phytochemical OCT2 Inhibitors and Their Functional Relevance to Cisplatin-Induced Cytotoxicity.Pharmaceutics · 2026Article
- Effect of SLC22A1 polymorphism on the pharmacokinetics of proguanil in Korean: A semi-physiologic population pharmacokinetic approach.Clinical and translational science · 2024Article
- Magnitude of Drug-Drug Interactions in Special Populations.Pharmaceutics · 2022Review
- Assessing the Roles of Molecular Markers of Antimalarial Drug Resistance and the Host Pharmacogenetics in Drug-Resistant Malaria.Journal of tropical medicine · 2022Review
- Functional inhibition of Oct leads to HNF4α upregulation.Experimental and therapeutic medicine · 2021Article
- Transport of Drugs and Endogenous Compounds Mediated by Human OCT1: Studies in Single- and Double-Transfected Cell Models.Frontiers in pharmacology · 2021Review
- Drug-Drug Interactions at Organic Cation Transporter 1.Frontiers in pharmacology · 2021Review
- Completing the Enalaprilat Excretion Pathway-Renal Handling by the Proximal Tubule.Pharmaceutics · 2020Article
- Genetic Heterogeneity of SLC22 Family of Transporters in Drug Disposition.Journal of personalized medicine · 2018Review
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMalaria, HIV/AIDS, and tuberculosis endemic areas show considerable geographical overlap, leading to incidence of co-infections. This requires treatment with multiple drugs, potentially causing adverse drug-drug interactions (DDIs). As anti-malarials are generally positively charged at physiological pH, they are likely to interact with human organic cation transporters 1 and 2 (OCT1 and OCT2). These transporters are involved in the uptake of drugs into hepatocytes and proximal tubule cells for subsequent metabolic conversion or elimination. This efflux of cationic drugs from hepatocytes and proximal tubule cells into bile and urine can be mediated by multidrug and toxin extrusion 1 and 2-K (MATE1 and MATE2-K) transporters, respectively.
methodsHere, the interaction of anti-malarials with these transporters was studied in order to predict potential DDIs. Using baculovirus-transduced HEK293 cells transiently expressing human OCT1, OCT2, MATE1 and MATE2K uptake and inhibition was studied by a range of anti-malarials.
resultsAmodiaquine, proguanil, pyrimethamine and quinine were the most potent inhibitors of 4-(4-(dimethylamino)styryl)-N-methylpyridinium iodide (ASP) transport, a known substrate of OCT1/2, resulting in half maximal inhibitory concentrations (IC
conclusionAnti-malarials can reduce OCT1 and OCT2 transport activity in vitro. Furthermore, proguanil and cycloguanil were found to be substrates of OCT1, OCT2, MATE1 and MATE2-K, highlighting the importance of these transporters in distribution and excretion. As these compounds shares substrate overlap with metformin DDIs can be anticipated during concurrent treatment.
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