{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T14:09:20Z","timestamp":1791036560999,"version":"4.1.0"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Malar J"],"published-print":{"date-parts":[[2011,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Tafenoquine is an 8-aminoquinoline being developed for radical cure (blood and liver stage elimination) of <jats:italic>Plasmodium vivax<\/jats:italic>. During monotherapy treatment, the compound exhibits slow parasite and fever clearance times, and toxicity in glucose-6-phosphate dehydrogenase (G6PD) deficiency is a concern. Combination with other antimalarials may mitigate these concerns.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>In 2005, the radical curative efficacy of tafenoquine combinations was investigated in <jats:italic>Plasmodium cynomolgi<\/jats:italic>-infected na\u00efve Indian-origin Rhesus monkeys. In the first cohort, groups of two monkeys were treated with a three-day regimen of tafenoquine at different doses alone and in combination with a three-day chloroquine regimen to determine the minimum curative dose (MCD). In the second cohort, the radical curative efficacy of a single-day regimen of tafenoquine-mefloquine was compared to that of two three-day regimens comprising tafenoquine at its MCD with chloroquine or artemether-lumefantrine in groups of six monkeys. In a final cohort, the efficacy of the MCD of tafenoquine against hypnozoites alone and in combination with chloroquine was investigated in groups of six monkeys after quinine pre-treatment to eliminate asexual parasites. Plasma tafenoquine, chloroquine and desethylchloroquine concentrations were determined by LC-MS in order to compare doses of the drugs to those used clinically in humans.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>The total MCD of tafenoquine required in combination regimens for radical cure was ten-fold lower (1.8 mg\/kg <jats:italic>versus<\/jats:italic> 18 mg\/kg) than for monotherapy. This regimen (1.8 mg\/kg) was equally efficacious as monotherapy or in combination with chloroquine after quinine pre-treatment to eliminate asexual stages. The same dose of (1.8 mg\/kg) was radically curative in combination with artemether-lumefantrine. Tafenoquine was also radically curative when combined with mefloquine. The MCD of tafenoquine monotherapy for radical cure (18 mg\/kg) appears to be biologically equivalent to a 600-1200 mg dose in humans. At its MCD in combination with blood schizonticidal drugs (1.8 mg\/kg), the maximum observed plasma concentrations were substantially lower than (20-84 <jats:italic>versus<\/jats:italic> 550-1,100 ng\/ml) after administration of 1, 200 mg in clinical studies.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Ten-fold lower clinical doses of tafenoquine than used in prior studies may be effective against <jats:italic>P. vivax<\/jats:italic> hypnozoites if the drug is deployed in combination with effective blood-schizonticidal drugs.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1475-2875-10-212","type":"journal-article","created":{"date-parts":[[2011,7,30]],"date-time":"2011-07-30T06:25:50Z","timestamp":1312007150000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["Radical curative efficacy of tafenoquine combination regimens in Plasmodium cynomolgi-infected Rhesus monkeys (Macaca mulatta)"],"prefix":"10.1186","volume":"10","author":[{"given":"Geoffrey S","family":"Dow","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Montip","family":"Gettayacamin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pranee","family":"Hansukjariya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rawiwan","family":"Imerbsin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srawuth","family":"Komcharoen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jetsumon","family":"Sattabongkot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"Kyle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilbur","family":"Milhous","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Cozens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Kenworthy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jim","family":"Veazey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin","family":"Ohrt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2011,7,29]]},"reference":[{"key":"1795_CR1","doi-asserted-by":"crossref","first-page":"803","DOI":"10.2147\/TCRM.S1025","volume":"4","author":"GS Dow","year":"2008","unstructured":"Dow GS, Magill AJ, Ohrt C: Clinical development of new prophylactic drugs after the 5th Amendment to the Declaration of Helsinki. 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