{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T01:59:33Z","timestamp":1792202373144,"version":"4.4.0"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Malar J"],"published-print":{"date-parts":[[2014,12]]},"DOI":"10.1186\/1475-2875-13-2","type":"journal-article","created":{"date-parts":[[2014,1,3]],"date-time":"2014-01-03T16:01:23Z","timestamp":1388764883000},"source":"Crossref","is-referenced-by-count":69,"title":["Tafenoquine and NPC-1161B require CYP 2D metabolism for anti-malarial activity: implications for the 8-aminoquinoline class of anti-malarial compounds"],"prefix":"10.1186","volume":"13","author":[{"given":"Sean R","family":"Marcsisin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason C","family":"Sousa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory A","family":"Reichard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Caridha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norma","family":"Roncal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronan","family":"McNulty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio","family":"Careagabarja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J","family":"Sciotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason W","family":"Bennett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor E","family":"Zottig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Deye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qigui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Read","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Hickman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N P Dhammika","family":"Nanayakkara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larry A","family":"Walker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Melendez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon S","family":"Pybus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2014,1,3]]},"reference":[{"key":"3077_CR1","doi-asserted-by":"publisher","first-page":"1336","DOI":"10.1086\/424663","volume":"39","author":"JK Baird","year":"2004","unstructured":"Baird JK, Hoffman SL: Primaquine therapy for malaria. Clin Infect Dis. 2004, 39: 1336-1345. 10.1086\/424663.","journal-title":"Clin Infect Dis"},{"key":"3077_CR2","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1093\/milmed\/134.9.802","volume":"134","author":"KH Rieckmann","year":"1969","unstructured":"Rieckmann KH, McNamara JV, Kass L, Powell RD: Gametocytocidal and sporontocidal effects of primaquine upon two strains of Plasmodium falciparum. Mil Med. 1969, 134: 802-819.","journal-title":"Mil Med"},{"key":"3077_CR3","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1186\/1475-2875-10-212","volume":"10","author":"GS Dow","year":"2011","unstructured":"Dow GS, Gettayacamin M, Hansukjariya P, Imerbsin R, Komcharoen S, Sattabongkot J, Kyle D, Milhous W, Cozens S, Kenworthy D, Miller A, Veazey J, Ohrt C: Radical curative efficacy of tafenoquine combination regimens in Plasmodium cynomolgi-infected Rhesus monkeys (Macaca mulatta). Malar J. 2011, 10: 212-10.1186\/1475-2875-10-212.","journal-title":"Malar J"},{"key":"3077_CR4","doi-asserted-by":"publisher","first-page":"e37166","DOI":"10.1371\/journal.pone.0037166","volume":"7","author":"RJ Maude","year":"2012","unstructured":"Maude RJ, Socheat D, Nguon C, Saroth P, Dara P, Li G, Song J, Yeung S, Dondorp AM, Day NP, White NJ, White LJ: Optimising strategies for Plasmodium falciparum malaria elimination in Cambodia: primaquine, mass drug administration and artemisinin resistance. PLoS One. 2012, 7: e37166-10.1371\/journal.pone.0037166.","journal-title":"PLoS One"},{"key":"3077_CR5","volume-title":"Eur J Drug Metab Pharmacokinet","author":"X Jin","year":"2013","unstructured":"Jin X, Pybus BS, Marcsisin SR, Logan T, Luong TL, Sousa J, Matlock N, Collazo V, Asher C, Carroll D, Olmeda R, Walker LA, Kozar MP, Melendez V: An LC-MS based study of the metabolic profile of primaquine, an 8-aminoquinoline antiparasitic drug, with an in vitro primary human hepatocyte culture model. Eur J Drug Metab Pharmacokinet. 2013, [Epub ahead of print] doi: 10.1007\/s13318-013-0139-8"},{"key":"3077_CR6","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1186\/1475-2875-12-212","volume":"12","author":"BS Pybus","year":"2013","unstructured":"Pybus BS, Marcsisin SR, Jin X, Deye G, Sousa JC, Li Q, Caridha D, Zeng Q, Reichard GA, Ockenhouse C, Bennett J, Walker LA, Ohrt C, Melendez V: The metabolism of primaquine to its active metabolite is dependent on CYP 2D6. Malar J. 2013, 12: 212-10.1186\/1475-2875-12-212.","journal-title":"Malar J"},{"key":"3077_CR7","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1186\/1475-2875-11-259","volume":"11","author":"BS Pybus","year":"2012","unstructured":"Pybus BS, Sousa JC, Jin X, Ferguson JA, Christian RE, Barnhart R, Vuong C, Sciotti RJ, Reichard GA, Kozar MP, Walker LA, Ohrt C, Melendez V: CYP450 phenotyping and accurate mass identification of metabolites of the 8-aminoquinoline, anti-malarial drug primaquine. Malar J. 2012, 11: 259-10.1186\/1475-2875-11-259.","journal-title":"Malar J"},{"key":"3077_CR8","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1016\/S0940-2993(99)80010-4","volume":"51","author":"L Constantino","year":"1999","unstructured":"Constantino L, Paixao P, Moreira R, Portela MJ, Do Rosario VE, Iley J: Metabolism of primaquine by liver homogenate fractions. Evidence for monoamine oxidase and cytochrome P450 involvement in the oxidative deamination of primaquine to carboxyprimaquine. Exp Toxicol Pathol. 1999, 51: 299-303. 10.1016\/S0940-2993(99)80010-4.","journal-title":"Exp Toxicol Pathol"},{"key":"3077_CR9","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.taap.2009.07.012","volume":"241","author":"S Ganesan","year":"2009","unstructured":"Ganesan S, Tekwani BL, Sahu R, Tripathi LM, Walker LA: Cytochrome P(450)-dependent toxic effects of primaquine on human erythrocytes. Toxicol Appl Pharmacol. 2009, 241: 14-22. 10.1016\/j.taap.2009.07.012.","journal-title":"Toxicol Appl Pharmacol"},{"key":"3077_CR10","doi-asserted-by":"crossref","first-page":"6848","DOI":"10.1016\/S0021-9258(19)50504-X","volume":"267","author":"J Vasquez-Vivar","year":"1992","unstructured":"Vasquez-Vivar J, Augusto O: Hydroxylated metabolites of the antimalarial drug primaquine. Oxidation and redox cycling. J Biol Chem. 1992, 267: 6848-6854.","journal-title":"J Biol Chem"},{"key":"3077_CR11","doi-asserted-by":"publisher","first-page":"2791","DOI":"10.1016\/0006-2952(88)90042-1","volume":"37","author":"O Augusto","year":"1988","unstructured":"Augusto O, Schreiber J, Mason RP: Direct ESR detection of a free radical intermediate during the peroxidase-catalyzed oxidation of the antimalarial drug primaquine. Biochem Pharmacol. 1988, 37: 2791-2797. 10.1016\/0006-2952(88)90042-1.","journal-title":"Biochem Pharmacol"},{"key":"3077_CR12","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/0003-9861(86)90103-7","volume":"244","author":"O Augusto","year":"1986","unstructured":"Augusto O, Weingrill CL, Schreier S, Amemiya H: Hydroxyl radical formation as a result of the interaction between primaquine and reduced pyridine nucleotides. Catalysis by hemoglobin and microsomes. Arch Biochem Biophys. 1986, 244: 147-155. 10.1016\/0003-9861(86)90103-7.","journal-title":"Arch Biochem Biophys"},{"key":"3077_CR13","doi-asserted-by":"publisher","first-page":"133","DOI":"10.3109\/00498259309059369","volume":"23","author":"S Morais Mda","year":"1993","unstructured":"Morais Mda S, Augusto O: Peroxidation of the antimalarial drug primaquine: characterization of a benzidine-like metabolite with methaemoglobin-forming activity. Xenobiotica. 1993, 23: 133-139. 10.3109\/00498259309059369.","journal-title":"Xenobiotica"},{"key":"3077_CR14","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1016\/0006-2952(94)90022-1","volume":"47","author":"J Vasquez-Vivar","year":"1994","unstructured":"Vasquez-Vivar J, Augusto O: Oxidative activity of primaquine metabolites on rat erythrocytes in vitro and in vivo. Biochem Pharmacol. 1994, 47: 309-316. 10.1016\/0006-2952(94)90022-1.","journal-title":"Biochem Pharmacol"},{"key":"3077_CR15","doi-asserted-by":"publisher","first-page":"1381","DOI":"10.1056\/NEJMc1301936","volume":"369","author":"JW Bennett","year":"2013","unstructured":"Bennett JW, Pybus BS, Yadava A, Tosh D, Sousa JC, McCarthy WF, Deye G, Melendez V, Ockenhouse CF: Primaquine failure and cytochrome P-450 2D6 in Plasmodium vivax malaria. N Engl J Med. 2013, 369: 1381-1382. 10.1056\/NEJMc1301936.","journal-title":"N Engl J Med"},{"key":"3077_CR16","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1007\/PL00000897","volume":"58","author":"P Anzenbacher","year":"2001","unstructured":"Anzenbacher P, Anzenbacherova E: Cytochromes P450 and metabolism of xenobiotics. Cell Mol Life Sci. 2001, 58: 737-747. 10.1007\/PL00000897.","journal-title":"Cell Mol Life Sci"},{"key":"3077_CR17","doi-asserted-by":"publisher","first-page":"689","DOI":"10.2165\/11318030-000000000-00000","volume":"48","author":"SF Zhou","year":"2009","unstructured":"Zhou SF: Polymorphism of human cytochrome P450 2D6 and its clinical significance: Part I. Clin Pharmacokinet. 2009, 48: 689-723. 10.2165\/11318030-000000000-00000.","journal-title":"Clin Pharmacokinet"},{"key":"3077_CR18","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1634\/theoncologist.11-2-126","volume":"11","author":"S Bernard","year":"2006","unstructured":"Bernard S, Neville KA, Nguyen AT, Flockhart DA: Interethnic differences in genetic polymorphisms of CYP2D6 in the U.S. population: clinical implications. Oncologist. 2006, 11: 126-135. 10.1634\/theoncologist.11-2-126.","journal-title":"Oncologist"},{"key":"3077_CR19","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1016\/j.tiv.2005.04.001","volume":"19","author":"A Bogni","year":"2005","unstructured":"Bogni A, Monshouwer M, Moscone A, Hidestrand M, Ingelman-Sundberg M, Hartung T, Coecke S: Substrate specific metabolism by polymorphic cytochrome P450 2D6 alleles. Toxicol In Vitro. 2005, 19: 621-629. 10.1016\/j.tiv.2005.04.001.","journal-title":"Toxicol In Vitro"},{"key":"3077_CR20","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1038\/sj.tpj.6500285","volume":"5","author":"M Ingelman-Sundberg","year":"2005","unstructured":"Ingelman-Sundberg M: Genetic polymorphisms of cytochrome P450 2D6 (CYP2D6): clinical consequences, evolutionary aspects and functional diversity. Pharmacogenomics J. 2005, 5: 6-13. 10.1038\/sj.tpj.6500285.","journal-title":"Pharmacogenomics J"},{"key":"3077_CR21","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1124\/mol.111.075192","volume":"81","author":"N Scheer","year":"2012","unstructured":"Scheer N, Kapelyukh Y, McEwan J, Beuger V, Stanley LA, Rode A, Wolf CR: Modeling human cytochrome P450 2D6 metabolism and drug-drug interaction by a novel panel of knockout and humanized mouse lines. Mol Pharmacol. 2012, 81: 63-72. 10.1124\/mol.111.075192.","journal-title":"Mol Pharmacol"},{"key":"3077_CR22","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.1086\/424508","volume":"39","author":"DS Walsh","year":"2004","unstructured":"Walsh DS, Wilairatana P, Tang DB, Heppner DG, Brewer TG, Krudsood S, Silachamroon U, Phumratanaprapin W, Siriyanonda D, Looareesuwan S: Randomized trial of 3-dose regimens of tafenoquine (WR238605) versus low-dose primaquine for preventing Plasmodium vivax malaria relapse. Clin Infect Dis. 2004, 39: 1095-1103. 10.1086\/424508.","journal-title":"Clin Infect Dis"},{"key":"3077_CR23","doi-asserted-by":"publisher","first-page":"1282","DOI":"10.1086\/315034","volume":"180","author":"DS Walsh","year":"1999","unstructured":"Walsh DS, Looareesuwan S, Wilairatana P, Heppner DG, Tang DB, Brewer TG, Chokejindachai W, Viriyavejakul P, Kyle DE, Milhous WK, Schuster BG, Horton J, Braitman DJ, Brueckner RP: Randomized dose-ranging study of the safety and efficacy of WR 238605 (Tafenoquine) in the prevention of relapse of Plasmodium vivax malaria in Thailand. J Infect Dis. 1999, 180: 1282-1287. 10.1086\/315034.","journal-title":"J Infect Dis"},{"key":"3077_CR24","doi-asserted-by":"publisher","first-page":"1456","DOI":"10.1086\/424468","volume":"190","author":"DS Walsh","year":"2004","unstructured":"Walsh DS, Eamsila C, Sasiprapha T, Sangkharomya S, Khaewsathien P, Supakalin P, Tang DB, Jarasrumgsichol P, Cherdchu C, Edstein MD, Rieckmann KH, Brewer TG: Efficacy of monthly tafenoquine for prophylaxis of Plasmodium vivax and multidrug-resistant P. falciparum malaria. J Infect Dis. 2004, 190: 1456-1463. 10.1086\/424468.","journal-title":"J Infect Dis"},{"key":"3077_CR25","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1086\/367542","volume":"36","author":"BR Hale","year":"2003","unstructured":"Hale BR, Owusu-Agyei S, Fryauff DJ, Koram KA, Adjuik M, Oduro AR, Prescott WR, Baird JK, Nkrumah F, Ritchie TL, Franke ED, Binka FN, Horton J, Hoffman SL: A randomized, double-blind, placebo-controlled, dose-ranging trial of tafenoquine for weekly prophylaxis against Plasmodium falciparum. Clin Infect Dis. 2003, 36: 541-549. 10.1086\/367542.","journal-title":"Clin Infect Dis"},{"key":"3077_CR26","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.1016\/j.trstmh.2008.04.024","volume":"102","author":"NJ Elmes","year":"2008","unstructured":"Elmes NJ, Nasveld PE, Kitchener SJ, Kocisko DA, Edstein MD: The efficacy and tolerability of three different regimens of tafenoquine versus primaquine for post-exposure prophylaxis of Plasmodium vivax malaria in the Southwest Pacific. Trans R Soc Trop Med Hyg. 2008, 102: 1095-1101. 10.1016\/j.trstmh.2008.04.024.","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"3077_CR27","doi-asserted-by":"publisher","first-page":"1495","DOI":"10.1124\/dmd.105.005488","volume":"33","author":"SL Miksys","year":"2005","unstructured":"Miksys SL, Cheung C, Gonzalez FJ, Tyndale RF: Human CYP2D6 and mouse CYP2Ds: organ distribution in a humanized mouse model. Drug Metab Dispos. 2005, 33: 1495-1502. 10.1124\/dmd.105.005488.","journal-title":"Drug Metab Dispos"},{"key":"3077_CR28","doi-asserted-by":"publisher","first-page":"691","DOI":"10.2217\/pgs.12.27","volume":"13","author":"CM Walko","year":"2012","unstructured":"Walko CM, McLeod H: Use of CYP2D6 genotyping in practice: tamoxifen dose adjustment. Pharmacogenomics. 2012, 13: 691-697. 10.2217\/pgs.12.27.","journal-title":"Pharmacogenomics"},{"key":"3077_CR29","doi-asserted-by":"publisher","first-page":"3225","DOI":"10.1128\/AAC.00777-06","volume":"50","author":"B Pradines","year":"2006","unstructured":"Pradines B, Mamfoumbi MM, Tall A, Sokhna C, Koeck JL, Fusai T, Mosnier J, Czarnecki E, Spiegel A, Trape JF, Kombila M, Rogier C: In vitro activity of tafenoquine against the asexual blood stages of Plasmodium falciparum isolates from Gabon, Senegal, and Djibouti. Antimicrob Agents Chemother. 2006, 50: 3225-3226. 10.1128\/AAC.00777-06.","journal-title":"Antimicrob Agents Chemother"},{"key":"3077_CR30","doi-asserted-by":"publisher","first-page":"e1001169","DOI":"10.1371\/journal.pmed.1001169","volume":"9","author":"M Delves","year":"2012","unstructured":"Delves M, Plouffe D, Scheurer C, Meister S, Wittlin S, Winzeler EA, Sinden RE, Leroy D: The activities of current antimalarial drugs on the life cycle stages of Plasmodium: a comparative study with human and rodent parasites. PLoS Med. 2012, 9: e1001169-10.1371\/journal.pmed.1001169.","journal-title":"PLoS Med"},{"key":"3077_CR31","doi-asserted-by":"publisher","first-page":"802","DOI":"10.3201\/eid1905.121852","volume":"19","author":"AT Bright","year":"2013","unstructured":"Bright AT, Alenazi T, Shokoples S, Tarning J, Paganotti GM, White NJ, Houston S, Winzeler EA, Yanow SK: Genetic analysis of primaquine tolerance in a patient with relapsing vivax malaria. Emerg Infect Dis. 2013, 19: 802-805. 10.3201\/eid1905.121852.","journal-title":"Emerg Infect Dis"},{"key":"3077_CR32","doi-asserted-by":"publisher","first-page":"63","DOI":"10.3109\/00365548.2013.822093","volume":"46","author":"K Langholz Kristensen","year":"2013","unstructured":"Langholz Kristensen K, Dragsted UB: Recurrent Plasmodium vivax malaria due to dose-dependent primaquine resistance: a case report. Scand J Infect Dis. 2013, 46: 63-65.","journal-title":"Scand J Infect Dis"},{"key":"3077_CR33","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1186\/1475-2875-10-351","volume":"10","author":"D Fernando","year":"2011","unstructured":"Fernando D, Rodrigo C, Rajapakse S: Primaquine in vivax malaria: an update and review on management issues. Malar J. 2011, 10: 351-10.1186\/1475-2875-10-351.","journal-title":"Malar J"}],"container-title":["Malaria Journal"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1475-2875-13-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,21]],"date-time":"2022-03-21T10:35:42Z","timestamp":1647858942000},"score":1,"resource":{"primary":{"URL":"https:\/\/malariajournal.biomedcentral.com\/articles\/10.1186\/1475-2875-13-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,1,3]]},"references-count":33,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2014,12]]}},"alternative-id":["3077"],"URL":"https:\/\/doi.org\/10.1186\/1475-2875-13-2","relation":{},"ISSN":["1475-2875"],"issn-type":[{"value":"1475-2875","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,1,3]]},"article-number":"2"}}