{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T04:59:08Z","timestamp":1781067548567,"version":"3.54.1"},"reference-count":41,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Biochemical Pharmacology"],"published-print":{"date-parts":[[2026,1]]},"DOI":"10.1016\/j.bcp.2025.117539","type":"journal-article","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T09:58:08Z","timestamp":1763373488000},"page":"117539","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"P2","title":["The impact of acacetin on proguanil metabolism: An in vitro and in vivo study"],"prefix":"10.1016","volume":"243","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-3673-4248","authenticated-orcid":false,"given":"Haoxin","family":"Fu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiqi","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiqi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruibin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yige","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheli","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bcp.2025.117539_b0005","unstructured":"C.f.D. Control, Prevention, CDC yellow book 2020: health information for international travel, Oxford University Press2019."},{"key":"10.1016\/j.bcp.2025.117539_b0010","unstructured":"W.H. Organization, World Malaria Report 2018, World Health Organization, Geneva, Switzerland, 2018."},{"issue":"1","key":"10.1016\/j.bcp.2025.117539_b0015","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pmed.1000221","article-title":"Quantifying the number of pregnancies at risk of malaria in 2007: a demographic study","volume":"7","author":"Dellicour","year":"2010","journal-title":"PLoS Med."},{"key":"10.1016\/j.bcp.2025.117539_b0020","first-page":"1450","article-title":"Rolling back malaria: action or rhetoric?","author":"Breman","year":"2000","journal-title":"SciELO Public Health"},{"issue":"4286","key":"10.1016\/j.bcp.2025.117539_b0025","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1038\/1681080a0","article-title":"A metabolite of \u2018Paludrine\u2019with high antimalarial activity","volume":"168","author":"Carrington","year":"1951","journal-title":"Nature"},{"key":"10.1016\/j.bcp.2025.117539_b0030","unstructured":"W.H. Organization, WHO Model Formulary 2008, World Health Organization, Geneva, Switzerland, 2009."},{"key":"10.1016\/j.bcp.2025.117539_b0035","unstructured":"T.A.S.o.H.-S. Pharmacists, Atovaquone and Proguanil Hydrochloride, 2016. https:\/\/www.drugs.com\/monograph\/atovaquone-proguanil.html. (Accessed 8 December 2016."},{"issue":"6","key":"10.1016\/j.bcp.2025.117539_b0040","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/0035-9203(94)90233-X","article-title":"Multiresistant falciparum malaria cured using atovaquone and proguanil","volume":"88","author":"Blanchard","year":"1994","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"issue":"2","key":"10.1016\/j.bcp.2025.117539_b0045","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/S0035-9203(98)90749-0","article-title":"Efficacy and pharmacokinetics of atovaquone and proguanil in children with multidrug-resistant Plasmodium falciparum malaria","volume":"92","author":"Sabchareon","year":"1998","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"issue":"7","key":"10.1016\/j.bcp.2025.117539_b0050","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1086\/322694","article-title":"Malarone International Study, Atovaquone-proguanil versus mefloquine for malaria prophylaxis in nonimmune travelers: results from a randomized, double-blind study","volume":"33","author":"Overbosch","year":"2001","journal-title":"Clin. Infect. Dis."},{"issue":"4","key":"10.1016\/j.bcp.2025.117539_b0055","doi-asserted-by":"crossref","first-page":"521","DOI":"10.4269\/ajtmh.1999.60.521","article-title":"A randomized, double-blind, placebo-controlled field trial to determine the efficacy and safety of Malarone (atovaquone\/proguanil) for the prophylaxis of malaria in Zambia","volume":"60","author":"Sukwa","year":"1999","journal-title":"Am. J. Trop. Med. Hyg."},{"issue":"2","key":"10.1016\/j.bcp.2025.117539_b0060","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1111\/j.1365-2125.1990.tb03777.x","article-title":"In vitro metabolism of the biguanide antimalarials in human liver microsomes: evidence for a role of the mephenytoin hydroxylase (P450 MP) enzyme","volume":"30","author":"Helsby","year":"1990","journal-title":"Br. J. Clin. Pharmacol."},{"issue":"6","key":"10.1016\/j.bcp.2025.117539_b0065","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1111\/j.1365-2125.1991.tb05594.x","article-title":"The activation of the biguanide antimalarial proguanil co\u2010segregates with the mephenytoin oxidation polymorphism\u2010a panel study","volume":"31","author":"Ward","year":"1991","journal-title":"Br. J. Clin. Pharmacol."},{"issue":"3","key":"10.1016\/j.bcp.2025.117539_b0070","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/0009-9236(95)90241-4","article-title":"Comparison of chloroguanide and mephenytoin for the in vivo assessment of genetically determined CYP2C19 activity in humans","volume":"58","author":"Partovian","year":"1995","journal-title":"Clin. Pharmacol. Ther."},{"issue":"6","key":"10.1016\/j.bcp.2025.117539_b0075","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1046\/j.1365-2125.1997.00596.x","article-title":"Association between CYP2C19 genotype and proguanil oxidative polymorphism","volume":"43","author":"Coller","year":"1997","journal-title":"Br. J. Clin. Pharmacol."},{"issue":"5","key":"10.1016\/j.bcp.2025.117539_b0080","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1046\/j.1365-2125.1998.00807.x","article-title":"Relationship between proguanil metabolic ratio and CYP2C19 genotype in a Caucasian population","volume":"46","author":"Hoskins","year":"1998","journal-title":"Br. J. Clin. Pharmacol."},{"issue":"8\u20139","key":"10.1016\/j.bcp.2025.117539_b0085","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1007\/s00228-003-0665-4","article-title":"Concordance between proguanil phenotype and CYP2C19 genotype in Chinese","volume":"59","author":"Hoskins","year":"2003","journal-title":"Eur. J. Clin. Pharmacol."},{"issue":"6","key":"10.1016\/j.bcp.2025.117539_b0090","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1111\/j.1365-2125.1989.tb03440.x","article-title":"Inter-subject variability in the metabolism of proguanil to the active metabolite cycloguanil in man","volume":"27","author":"Ward","year":"1989","journal-title":"Br. J. Clin. Pharmacol."},{"issue":"4","key":"10.1016\/j.bcp.2025.117539_b0095","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1111\/j.1365-2125.1990.tb03818.x","article-title":"The pharmacokinetics and activation of proguanil in man: consequences of variability in drug metabolism","volume":"30","author":"Helsby","year":"1990","journal-title":"Br. J. Clin. Pharmacol."},{"issue":"22","key":"10.1016\/j.bcp.2025.117539_b0100","doi-asserted-by":"crossref","first-page":"15419","DOI":"10.1016\/S0021-9258(17)40694-6","article-title":"The major genetic defect responsible for the polymorphism of S-mephenytoin metabolism in humans","volume":"269","author":"de Morais","year":"1994","journal-title":"J. Biol. Chem."},{"issue":"4","key":"10.1016\/j.bcp.2025.117539_b0105","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1016\/S0026-895X(25)09788-3","article-title":"Identification of a new genetic defect responsible for the polymorphism of (S)-mephenytoin metabolism in Japanese","volume":"46","author":"De Morais","year":"1994","journal-title":"Mol. Pharmacol."},{"issue":"2","key":"10.1016\/j.bcp.2025.117539_b0110","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1097\/FPC.0b013e32831ebb30","article-title":"Pharmacogenetic variation at CYP2C9, CYP2C19, and CYP2D6 at global and microgeographic scales","volume":"19","author":"Sistonen","year":"2009","journal-title":"Pharmacogenet. Genomics"},{"issue":"1","key":"10.1016\/j.bcp.2025.117539_b0115","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.clpt.2005.10.002","article-title":"A common novel CYP2C19 gene variant causes ultrarapid drug metabolism relevant for the drug response to proton pump inhibitors and antidepressants","volume":"79","author":"Sim","year":"2006","journal-title":"Clin. Pharmacol. Ther."},{"issue":"11","key":"10.1016\/j.bcp.2025.117539_b0120","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1111\/1440-1681.12297","article-title":"CYP2C19* 17 increases clopidogrel\u2010mediated platelet inhibition but does not alter the pharmacokinetics of the active metabolite of clopidogrel","volume":"41","author":"Pedersen","year":"2014","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"issue":"3","key":"10.1016\/j.bcp.2025.117539_b0125","doi-asserted-by":"crossref","first-page":"536","DOI":"10.3109\/13880209.2015.1052885","article-title":"Isolation of major phenolics from Launaea spinosa and their protective effect on HepG2 cells damaged with t-BHP","volume":"54","author":"Abdallah","year":"2016","journal-title":"Pharm. Biol."},{"key":"10.1016\/j.bcp.2025.117539_b0130","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.phytol.2019.04.021","article-title":"Acacetin\u2014a simple flavone exhibiting diverse pharmacological activities","volume":"32","author":"Semwal","year":"2019","journal-title":"Phytochem. Lett."},{"key":"10.1016\/j.bcp.2025.117539_b0135","doi-asserted-by":"crossref","DOI":"10.1016\/j.fct.2020.111708","article-title":"Acacetin, a flavone with diverse therapeutic potential in cancer, inflammation, infections and other metabolic disorders","volume":"145","author":"Singh","year":"2020","journal-title":"Food Chem. Toxicol."},{"issue":"19","key":"10.1016\/j.bcp.2025.117539_b0140","doi-asserted-by":"crossref","first-page":"5530","DOI":"10.1021\/acs.jafc.9b00330","article-title":"A systematic study of the metabolites of dietary acacetin in vivo and in vitro based on UHPLC-Q-TOF-MS\/MS analysis","volume":"67","author":"Yin","year":"2019","journal-title":"J. Agric. Food Chem."},{"key":"10.1016\/j.bcp.2025.117539_b0145","doi-asserted-by":"crossref","DOI":"10.1016\/j.cbi.2020.109147","article-title":"Evaluation of acacetin inhibition potential against cytochrome P450 in vitro and in vivo","volume":"329","author":"Zhou","year":"2020","journal-title":"Chem. Biol. Interact."},{"key":"10.1016\/j.bcp.2025.117539_b0150","doi-asserted-by":"crossref","first-page":"591","DOI":"10.3389\/fphar.2019.00591","article-title":"Enzymatic activities of CYP3A4 allelic variants on quinine 3-hydroxylation in vitro","volume":"10","author":"Zhou","year":"2019","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.bcp.2025.117539_b0155","doi-asserted-by":"crossref","first-page":"513","DOI":"10.2147\/DDDT.S160316","article-title":"Inhibitory effect of celecoxib on agomelatine metabolism in vitro and in vivo","volume":"12","author":"He","year":"2018","journal-title":"Drug Des. Devel. Ther."},{"key":"10.1016\/j.bcp.2025.117539_b0160","doi-asserted-by":"crossref","DOI":"10.1016\/j.jpba.2022.114976","article-title":"Metabolites identification for major active components of Agastache rugosa in rat by UPLC-Orbitap-MS: Comparison of the difference between metabolism as a single component and as a component in a multi-component extract","volume":"220","author":"Jang","year":"2022","journal-title":"J. Pharm. Biomed. Anal."},{"issue":"1","key":"10.1016\/j.bcp.2025.117539_b0165","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.92587","article-title":"Assessing drug efficacy against Plasmodium falciparum liver stages in vivo","volume":"3","author":"Flannery","year":"2018","journal-title":"JCI Insight"},{"issue":"1","key":"10.1016\/j.bcp.2025.117539_b0170","doi-asserted-by":"crossref","first-page":"6817","DOI":"10.1038\/s41467-025-62063-8","article-title":"Nanozymes expanding the boundaries of biocatalysis","volume":"16","author":"Zhang","year":"2025","journal-title":"Nat. Commun."},{"issue":"6","key":"10.1016\/j.bcp.2025.117539_b0175","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1128\/AAC.43.6.1334","article-title":"A mechanism for the synergistic antimalarial action of atovaquone and proguanil","volume":"43","author":"Srivastava","year":"1999","journal-title":"Antimicrob. Agents Chemother."},{"issue":"2","key":"10.1016\/j.bcp.2025.117539_b0180","doi-asserted-by":"crossref","first-page":"208","DOI":"10.4269\/ajtmh.2007.76.208","article-title":"Atovaquone-proguanil: report from the CDC expert meeting on malaria chemoprophylaxis (II)","volume":"76","author":"Boggild","year":"2007","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"10.1016\/j.bcp.2025.117539_b0185","unstructured":"N.C.f.B. Information, PubChem Compound Summary for CID 6178111, Proguanil., 2025. https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/6178111. (Accessed 2025-09-03."},{"issue":"9","key":"10.1016\/j.bcp.2025.117539_b0190","doi-asserted-by":"crossref","first-page":"900","DOI":"10.2174\/138920011797470100","article-title":"Regioselective sulfation and glucuronidation of phenolics: insights into the structural basis","volume":"12","author":"Wu","year":"2011","journal-title":"Curr. Drug Metab."},{"issue":"1","key":"10.1016\/j.bcp.2025.117539_b0195","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1186\/s12936-017-2062-y","article-title":"Proguanil and cycloguanil are organic cation transporter and multidrug and toxin extrusion substrates","volume":"16","author":"van der Velden","year":"2017","journal-title":"Malar. J."},{"issue":"9","key":"10.1016\/j.bcp.2025.117539_b0200","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1002\/jat.4628","article-title":"Inhibitory effect of flavonoids on multidrug and toxin extrusion protein 1 function: implications for food\/herb-drug interaction and drug-induced kidney injury","volume":"44","author":"Duan","year":"2024","journal-title":"J. Appl. Toxicol."},{"key":"10.1016\/j.bcp.2025.117539_b0205","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.2147\/DDDT.S249308","article-title":"Inhibitory effect of lygodium root on the cytochrome p450 3a enzyme in vitro and in vivo","volume":"14","author":"Zhou","year":"2020","journal-title":"Drug Des. Devel. Ther."}],"container-title":["Biochemical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006295225008044?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006295225008044?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T04:18:35Z","timestamp":1781065115000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0006295225008044"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":41,"alternative-id":["S0006295225008044"],"URL":"https:\/\/doi.org\/10.1016\/j.bcp.2025.117539","relation":{},"ISSN":["0006-2952"],"issn-type":[{"value":"0006-2952","type":"print"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"The impact of acacetin on proguanil metabolism: An in vitro and in vivo study","name":"articletitle","label":"Article Title"},{"value":"Biochemical Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bcp.2025.117539","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"117539"}}