{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T02:17:55Z","timestamp":1777515475016,"version":"3.51.4"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,1,8]],"date-time":"2022-01-08T00:00:00Z","timestamp":1641600000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,1,8]],"date-time":"2022-01-08T00:00:00Z","timestamp":1641600000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100006507","name":"funda\u00e7\u00e3o oswaldo cruz","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006507","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Malar J"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Vivax malaria is a neglected disease. There is an irrefutable need for better treatments with higher acceptability and efficacy. The treatment efficacy is influenced by many factors, including bioavailability. Hence, a straightforward strategy to improve vivax malaria treatment efficacy is the deployment of good quality formulations of primaquine and chloroquine. As these treatments were developed more than 70\u00a0years ago, many of the available data on blood levels of both drugs are based on obsolete analytical methodologies or pharmaceutical formulations, which are not available anymore. Herein, the results of three bioequivalence studies are presented, providing individual pharmacokinetic data on chloroquine and primaquine of more than a hundred healthy volunteers and using up-to-date analytical methods.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Three trials were designed as a single centre, randomized, single dose, open label, fasting, crossover bioequivalence studies comparing a new coated chloroquine tablet to the uncoated tablet, and 5 and 15\u00a0mg primaquine formulations to either an international reference product or the currently distributed tablets. Plasma concentrations of chloroquine and primaquine were measured using a validated HPLC\u2013MS\/MS method in accordance with current international regulatory requirements for bio-analytical methods.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>In total, a hundred eleven healthy volunteers of both genders were included in the three studies (n\u2009=\u200932; 30 and 56 respectively). No serious adverse events occurred. Drugs levels were measured in 5,520 blood samples. The estimated ratio of the geometric means of Cmax, AUC0-t and AUC0-inf of test and reference drugs and their 90% CI for chloroquine 150\u00a0mg, primaquine 15\u00a0mg and primaquine 5\u00a0mg were: 95.33% (89.18; 101.90), 86. 85% (82.61; 91.31), and 84.45% (76.95; 92.67); 93.28% (81.76; 106.41), 94.52% (86.13; 103.73) and 93.93% (85.83; 102.79); 97.44% (90.60; 104.78), 93.70% (87.04; 100.87) and 91.36% (85.27; 97.89), respectively. As Cmax and AUC0-t 90% CI were within the acceptance interval of 80\u2013125% in all cases, the formulations tested were bioequivalent.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>In conclusion, the three studies provided detailed chloroquine and primaquine pharmacokinetic data in accordance with current regulatory standards. Together with other open data initiatives, this individual data may increase the accuracy of pharmacokinetic models guiding best dose, new combinations, regimens and formulations to optimize the current chloroquine and primaquine treatments for vivax malaria. The data presented here may support the deployment of high-quality drugs and evidence-based public health policies.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12936-021-04035-z","type":"journal-article","created":{"date-parts":[[2022,1,8]],"date-time":"2022-01-08T16:02:42Z","timestamp":1641657762000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Pharmacokinetics of chloroquine and primaquine in healthy volunteers"],"prefix":"10.1186","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9747-0222","authenticated-orcid":false,"given":"Andr\u00e9","family":"Daher","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas Pereira","family":"Pinto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"La\u00eds Bastos","family":"da Fonseca","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heliana Martins","family":"Pereira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diego Medeiros Dias","family":"da Silva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Let\u00edcia de S\u00e1 Fernandes Vallim","family":"da Silva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra Lanzillotta","family":"Esteves","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juliana J.","family":"Soares Medeiros","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge Souza","family":"Mendon\u00e7a","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,1,8]]},"reference":[{"key":"4035_CR1","unstructured":"WHO. 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Informed consent from all participants was acquired before the study initiation, as declared in the ethics and regulatory statement. All signed informed consent forms are kept for at least five years after the study end.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The confidentiality of the patients\u2019 records has been observed according to ethical regulations.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare following competing interests and financial disclosure: Alessandra Lanzillotta Esteves, Juliana J. Soares Medeiros, Jorge Souza Mendon\u00e7a are employees of the Institute of Drug Technology (Farmanguinhos), Oswaldo Cruz Foundation (Fiocruz), a Brazilian governmental institution of Ministry of Health. Farmanguinhos is the study sponsors. They were involved in the decision to publish and preparation of the manuscript. Farmanguinhos does not sell medicine on the market. The Brazilian Ministry of Health exclusively drives its drug production. These disclosures do not alter our adherence policies on sharing data and materials. There are no restrictions on the sharing of data and\/or materials.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"16"}}