{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T17:50:22Z","timestamp":1789062622739,"version":"build-2803163510"},"reference-count":48,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,7,2]],"date-time":"2020-07-02T00:00:00Z","timestamp":1593648000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004167","name":"Medicines for Malaria Venture","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004167","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000278","name":"Department for International Development, UK Government","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000278","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007843","name":"Direktoratet for Utviklingssamarbeid","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007843","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009099","name":"Irish Aid","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009099","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009022","name":"Newcrest Mining","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009022","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:p>Chloroquine has been used for the treatment of malaria for &gt;\u00a070\u00a0years; however, chloroquine pharmacokinetic (PK) and pharmacodynamic (PD) profile in <jats:italic>Plasmodium vivax<\/jats:italic> malaria is poorly understood. The objective of this study was to describe the PK\/PD relationship of chloroquine and its major metabolite, desethylchloroquine, in a <jats:italic>P. vivax<\/jats:italic> volunteer infection study. We analyzed data from 24 healthy subjects who were inoculated with blood\u2010stage <jats:italic>P. vivax<\/jats:italic> malaria and administered a standard treatment course of chloroquine. The PK of chloroquine and desethylchloroquine was described by a two\u2010compartment model with first\u2010order absorption and elimination. The relationship between plasma and whole blood concentrations of chloroquine and <jats:italic>P. vivax<\/jats:italic> parasitemia was characterized by a PK\/PD delayed response model, where the equilibration half\u2010lives were 32.7\u00a0hours (95% confidence interval (CI) 27.4\u201340.5) for plasma data and 24.1\u00a0hours (95% CI 19.0\u201332.7) for whole blood data. The estimated parasite multiplication rate was 17 folds per 48\u00a0hours (95% CI 14\u201320) and maximum parasite killing rate by chloroquine was 0.213\u00a0hour<jats:sup>\u22121<\/jats:sup> (95% CI 0.196\u20130.230), translating to a parasite clearance half\u2010life of 4.5\u00a0hours (95% CI 4.1\u20135.0) and a parasite reduction ratio of 400 every 48\u00a0hours (95% CI 320\u2013500). This is the first study that characterized the PK\/PD relationship between chloroquine plasma and whole blood concentrations and <jats:italic>P. vivax<\/jats:italic> clearance using a semimechanistic population PK\/PD modeling. This PK\/PD model can be used to optimize dosing scenarios and to identify optimal dosing regimens for chloroquine where resistance to chloroquine is increasing.<\/jats:p>","DOI":"10.1002\/cpt.1893","type":"journal-article","created":{"date-parts":[[2020,5,16]],"date-time":"2020-05-16T18:39:40Z","timestamp":1589654380000},"page":"1055-1066","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Population Pharmacokinetics and Pharmacodynamics of Chloroquine in a <i>Plasmodium vivax<\/i> Volunteer Infection Study"],"prefix":"10.1111","volume":"108","author":[{"given":"Azrin N.","family":"Abd\u2010Rahman","sequence":"first","affiliation":[{"name":"QIMR Berghofer Medical Research Institute Brisbane Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Marquart","sequence":"additional","affiliation":[{"name":"QIMR Berghofer Medical Research Institute Brisbane Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Gobeau","sequence":"additional","affiliation":[{"name":"Medicines for Malaria Venture Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"K\u00fcmmel","sequence":"additional","affiliation":[{"name":"IntiQuan GmbH Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie A.","family":"Simpson","sequence":"additional","affiliation":[{"name":"Centre for Epidemiology and Biostatistics Melbourne School of Population and Global Health The University of Melbourne Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Chalon","sequence":"additional","affiliation":[{"name":"Medicines for Malaria Venture Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg J.","family":"M\u00f6hrle","sequence":"additional","affiliation":[{"name":"Medicines for Malaria Venture Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James S.","family":"McCarthy","sequence":"additional","affiliation":[{"name":"QIMR Berghofer Medical Research Institute Brisbane Australia"},{"name":"University of Queensland Brisbane Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,7,2]]},"reference":[{"key":"e_1_2_10_1_1","unstructured":"World Health Organization.World Malaria Report 2019<https:\/\/www.who.int\/malaria\/publications\/world\u2010malaria\u2010report\u20102019\/en\/>. (2019)."},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(89)91792-3"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(89)92002-3"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(14)70855-2"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpddr.2017.03.003"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1988.tb03332.x"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1994.tb04354.x"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-008-0500-z"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01269-09"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.4103\/0253-7613.190720"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-016-1530-0"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-016-1181-1"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2017.05.011"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02476-17"},{"key":"e_1_2_10_15_1","article-title":"A Plasmodium vivax experimental human infection model for evaluating the efficacy of interventions","author":"Collins K.A.","journal-title":"J. Clin. Invest."},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jit394"},{"key":"e_1_2_10_17_1","volume-title":"R: A language and environment for statistical computing","author":"R Core Team","year":"2018"},{"key":"e_1_2_10_18_1","doi-asserted-by":"crossref","unstructured":"Wickham H.ggplot2: Elegant graphics for data analysis<https:\/\/ggplot2\u2010book.org\/> (2016).","DOI":"10.1007\/978-3-319-24277-4"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1080\/00034983.1984.11811868"},{"key":"e_1_2_10_20_1","first-page":"93","article-title":"In vitro activity of chloroquine, the two enantiomers of chloroquine, desethylchloroquine and pyronaridine against Plasmodium falciparum","volume":"22","author":"Fu S.","year":"1986","journal-title":"Br. J. Clin. Pharmacol."},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0035-9203(87)90175-1"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(84)91436-3"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1012299115260"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiw234"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007691-200312000-00005"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000000261"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00339-08"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00542151"},{"key":"e_1_2_10_29_1","first-page":"581","article-title":"Distribution of chloroquine in human blood fractions","volume":"10","author":"Nosal R.","year":"1988","journal-title":"Meth. Find Exp. Clin. Pharmacol."},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-4347(00)86110-1"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1983.tb01532.x"},{"key":"e_1_2_10_32_1","unstructured":"World Health Organization.Methods and techniques for assessing exposure to antimalarial drugs in clinical field studies<https:\/\/www.who.int\/malaria\/publications\/atoz\/9789241502061\/en\/> (2011)."},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007691-198506000-00013"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-018-2278-5"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01334-07"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-7-94"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0001772"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.44.6.1680-1685.2000"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-3156.2002.00948.x"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(15)00320-5"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1602250"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(18)30309-8"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01712-10"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41421-020-0156-0"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-020-0282-0"},{"key":"e_1_2_10_46_1","article-title":"In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102)","author":"Yao X.","journal-title":"Clin. Infect. Dis"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-3623(82)90110-0"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042-7158.1982.tb06211.x"}],"container-title":["Clinical Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcpt.1893","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.1893","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpt.1893","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.1893","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T13:37:51Z","timestamp":1699364271000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/cpt.1893"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,2]]},"references-count":48,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2020,11]]}},"alternative-id":["10.1002\/cpt.1893"],"URL":"https:\/\/doi.org\/10.1002\/cpt.1893","archive":["Portico"],"relation":{},"ISSN":["0009-9236","1532-6535"],"issn-type":[{"value":"0009-9236","type":"print"},{"value":"1532-6535","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,2]]},"assertion":[{"value":"2020-03-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-05-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-07-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}