{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T21:32:20Z","timestamp":1774560740316,"version":"3.50.1"},"reference-count":10,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T00:00:00Z","timestamp":1740441600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>Aim: To assess the impact of the CYP2C82 polymorphism on chloroquine and desethylchloroquine concentrations in patients with malaria caused by P. vivax. Methods: A prospective study was conducted on patients with malaria in an endemic area of the Amazon basin. Liquid chromatography was employed to measure the levels of chloroquine and desethylchloroquine, while molecular methods estimated the frequency of the CYP2C82 variant. Results: This study revealed that plasma levels of chloroquine were higher in patients with the CYP2C82 polymorphism compared to those without this variant. The difference in plasma levels ranged from 5% to 26.5%. Conversely, patients with the CYP2C82 polymorphism exhibited lower levels of desethylchloroquine. Conclusion: The findings of this study confirm the impairment of chloroquine metabolism by the CYP2C82 variant. However, it is noteworthy that in the dose regimen used for malaria treatment, these changes did not lead to toxic concentrations of the drug.<\/jats:p>","DOI":"10.3390\/ijerph22030336","type":"journal-article","created":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T03:40:12Z","timestamp":1740454812000},"page":"336","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Influence of CYP2C8 Polymorphism on the Exposure to Chloroquine in Patients with Malaria by Plasmodium vivax\u2014A Preliminary Study"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9363-5766","authenticated-orcid":false,"given":"Luann Wendel","family":"Pereira de Sena","sequence":"first","affiliation":[{"name":"College of Collective Health, Federal University of the South and Southeast of Para, Cidade Universitaria, Avenida dos Ip\u00eas s\/n, Maraba 68500000, Para, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0616-3543","authenticated-orcid":false,"given":"Hellen Thais","family":"Fuzii","sequence":"additional","affiliation":[{"name":"Tropical Medicine Center, Para Federal University, Generalissimo Deodoro Street 92, Belem 66074740, Para, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabiola Elizabeth","family":"Villanova","sequence":"additional","affiliation":[{"name":"Tropical Medicine Center, Para Federal University, Generalissimo Deodoro Street 92, Belem 66074740, Para, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda Gabryelle","family":"Nunes Cardoso Mello","sequence":"additional","affiliation":[{"name":"Pharmacy Faculty, Para Federal University, Campus Universitario do Guama, Augusto Correa Street 01, Belem 66074740, Para, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Pantoja Moreira","family":"de Sena","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Tropical Diseases, Para Federal University, Generalissimo Deodoro Street 92, Belem 66074740, Para, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle Val\u00e9ria","family":"Dias Ferreira","sequence":"additional","affiliation":[{"name":"Pharmacy Faculty, Para Federal University, Campus Universitario do Guama, Augusto Correa Street 01, Belem 66074740, Para, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4842-8762","authenticated-orcid":false,"given":"Jos\u00e9 Luiz","family":"Fernandes Vieira","sequence":"additional","affiliation":[{"name":"Pharmacy Faculty, Para Federal University, Campus Universitario do Guama, Augusto Correa Street 01, Belem 66074740, Para, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,25]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2015). Malaria: Guidelines for the Treatment."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"346853","DOI":"10.1155\/2015\/346853","article-title":"Side Effects of Chloroquine and Primaquine and Symptom Reduction in a Malaria Endemic Area (M\u00e2ncio Lima, Acre, Brazil)","volume":"2015","author":"Braga","year":"2015","journal-title":"Interdiscip. Perspect. Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1007\/s00296-021-04868-6","article-title":"Systemic toxicity of chloroquine and hydroxychloroquine: Prevalence, mechanisms, risk factors, prognostic and screening possibilities","volume":"41","author":"Muller","year":"2021","journal-title":"Rheumatol. Int."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e58631","DOI":"10.7554\/eLife.58631","article-title":"Concentration-dependent mortality of chloroquine in overdose","volume":"9","author":"Watson","year":"2020","journal-title":"Elife"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"257","DOI":"10.2165\/00003088-199631040-00003","article-title":"Clinical pharmacokinetics and metabolism of chloroquine. Focus on recent advancements","volume":"31","author":"Ducharme","year":"1996","journal-title":"Clin. Pharmacokinet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1124\/pr.115.011411","article-title":"Role of Cytochrome P450 2C8 in Drug Metabolism and Interactions","volume":"68","author":"Backman","year":"2016","journal-title":"Pharmacol. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1111\/bcpt.13492","article-title":"BCPT policy for experimental and clinical studies","volume":"128","author":"Bergmann","year":"2021","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1002\/bmc.3657","article-title":"An HPLC method with a diode array detector for the simultaneous quantification of chloroquine and desethylchloroquine in plasma and whole blood samples from Plasmodium vivax patients in Vietnam, using quinine as an internal standard","volume":"30","author":"Pham","year":"2016","journal-title":"Biomed. Chromatogr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/tpj.2010.89","article-title":"Global pharmacogenomics: Impact of population diversity on the distribution of polymorphisms in the CYP2C cluster among Brazilians","volume":"12","author":"Genro","year":"2012","journal-title":"Pharmacogenom. J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1186\/s12936-021-03620-6","article-title":"Influence of cytochrome P450 (CYP) 2C8 polymorphisms on the efficacy and tolerability of artesunate-amodiaquine treatment of uncomplicated Plasmodium falciparum malaria in Zanzibar","volume":"20","author":"Morris","year":"2021","journal-title":"Malar. J."}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/22\/3\/336\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:41:49Z","timestamp":1760028109000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/22\/3\/336"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,25]]},"references-count":10,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["ijerph22030336"],"URL":"https:\/\/doi.org\/10.3390\/ijerph22030336","relation":{},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,25]]}}}