{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:41:09Z","timestamp":1785415269459,"version":"3.56.0"},"reference-count":82,"publisher":"Bentham Science Publishers Ltd.","issue":"14","content-domain":{"domain":["eurekaselect.com"],"crossmark-restriction":true},"short-container-title":["CDM"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:sec>\n<jats:title>Background::<\/jats:title>\n<jats:p>In clinical practice, chloroquine and hydroxychloroquine are often co-administered\nwith other drugs in the treatment of malaria, chronic inflammatory diseases, and COVID-19. Therefore, their\nmetabolic properties and the effects on the activity of cytochrome P450 (P450, CYP) enzymes and drug transporters\nshould be considered when developing the most efficient treatments for patients.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods::<\/jats:title>\n<jats:p>Scientific literature on the interactions of chloroquine and hydroxychloroquine with human P450 enzymes\nand drug transporters, was searched using PUBMED.Gov (https:\/\/pubmed.ncbi.nlm.nih.gov\/) and the\nADME database (https:\/\/life-science.kyushu.fujitsu.com\/admedb\/).<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results::<\/jats:title>\n<jats:p>Chloroquine and hydroxychloroquine are metabolized by P450 1A2, 2C8, 2C19, 2D6, and 3A4\/5 in\nvitro and by P450s 2C8 and 3A4\/5 in vivo by N-deethylation. Chloroquine effectively inhibited P450 2D6 in\nvitro; however, in vivo inhibition was not apparent except in individuals with limited P450 2D6 activity. Chloroquine\nis both an inhibitor and inducer of the transporter MRP1 and is also a substrate of the Mate and MRP1\ntransport systems. Hydroxychloroquine also inhibited P450 2D6 and the transporter OATP1A2.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusions::<\/jats:title>\n<jats:p>Chloroquine caused a statistically significant decrease in P450 2D6 activity in vitro and in vivo,\nalso inhibiting its own metabolism by the enzyme. The inhibition indicates a potential for clinical drug-drug interactions\nwhen taken with other drugs that are predominant substrates of the P450 2D6. When chloroquine and\nhydroxychloroquine are used clinically with other drugs, substrates of P450 2D6 enzyme, attention should be\ngiven to substrate-specific metabolism by P450 2D6 alleles present in individuals taking the drugs.<\/jats:p>\n<\/jats:sec>","DOI":"10.2174\/1389200221999201208211537","type":"journal-article","created":{"date-parts":[[2020,12,9]],"date-time":"2020-12-09T09:48:21Z","timestamp":1607507301000},"page":"1127-1135","update-policy":"https:\/\/doi.org\/10.2174\/bsp_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Metabolism and Interactions of Chloroquine and Hydroxychloroquine with Human Cytochrome P450 Enzymes and Drug Transporters"],"prefix":"10.2174","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0970-1407","authenticated-orcid":true,"given":"Slobodan","family":"Rendic","sequence":"first","affiliation":[{"name":"Independent Scientist, Zagreb,Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7458-3048","authenticated-orcid":true,"given":"Frederick Peter","family":"Guengerich","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146,United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"965","reference":[{"key":"ref=1","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/S0049-0172(10)80012-5","volume":"23","author":"Fox R.I.","year":"1993","unstructured":"Fox R.I.; Mechanism of action of hydroxychloroquine as an antirheumatic drug. 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