{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T14:01:40Z","timestamp":1761487300593},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":2950,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2001,1]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>The antimalarial drug halofantrine can prolong the QT interval and this may be enhanced by prior use of mefloquine. This possible interaction has been investigated by examining the effects of halofantrine and mefloquine alone and in combination.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In anaesthetized rabbits (<jats:italic>n<\/jats:italic>=6 per group), halofantrine given as bolus doses of 1, 3, 10, and 30\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup> at 25\u2003min intervals dose\u2010dependently prolonged the rate\u2010corrected QT (QTc) interval from 313\u00b112\u2003ms pre\u2010drug to 410\u00b118\u2003ms after the highest dose. Similar doses of mefloquine did not alter QTc intervals significantly. The highest dose of mefloquine (30\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>) caused cardiac contractile failure.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Pretreatment with 3\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup> mefloquine 25\u2003min before the first dose of halofantrine potentiated the effects of all doses of halofantrine on QTc intervals.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The blood concentrations of halofantrine were two to six times higher in the group pretreated with mefloquine compared to the halofantrine alone group; e.g. 1.03\u00b10.17 and 0.16\u00b10.02 \u03bc<jats:sc>M<\/jats:sc> respectively after 1\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup> halofantrine. There was a significant correlation between blood halofantrine concentrations and QTc intervals (<jats:italic>r<\/jats:italic>=0.673). Even after making allowance for overestimation of the potency of halofantrine that may result from the hypokalaemia that is prevalent in anaesthetized rabbits, these effects occurred with concentrations of halofantrine that are found in clinical use.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These data indicate clearly that while mefloquine does not alter QTc intervals itself, it does enhance the effects of halofantrine by increasing the circulating concentration of halofantrine.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2001) <jats:bold>132<\/jats:bold>, 197\u2013204; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0703823\">10.1038\/sj.bjp.0703823<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0703823","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T21:06:00Z","timestamp":1106946360000},"page":"197-204","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Potentiation of halofantrine\u2010induced QTc prolongation by mefloquine: correlation with blood concentrations of halofantrine"],"prefix":"10.1111","volume":"132","author":[{"given":"Ian D","family":"Lightbown","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James P","family":"Lambert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geoffrey","family":"Edwards","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan J","family":"Coker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1056-8719(96)00145-1"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.1998.0664"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0701402"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1211\/0022357991772628"},{"key":"e_1_2_7_6_1","first-page":"565","article-title":"Effect of selected antimalarial drugs and inhibitors of cytochrome P\u2010450 3A4 on halofantrine metabolism by human liver microsomes","volume":"27","author":"BAUNE B.","year":"1999","journal-title":"Drug Metab. 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