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The anti-\n                    <jats:italic>Wolbachia<\/jats:italic>\n                    consortium (A\u00b7WOL:\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.a-wol.com\/\">http:\/\/www.a-wol.com\/<\/jats:ext-link>\n                    ) has identified a number of registered antibiotics that target the endosymbiotic bacterium,\n                    <jats:italic>Wolbachia,<\/jats:italic>\n                    delivering macrofilaricidal activity. Here we use pharmacokinetics\/pharmacodynamics (PK\/PD) analysis to rationally develop an anti-\n                    <jats:italic>Wolbachia<\/jats:italic>\n                    chemotherapy by linking drug exposure to pharmacological effect. We compare the pharmacokinetics and anti-\n                    <jats:italic>Wolbachia<\/jats:italic>\n                    efficacy in a murine\n                    <jats:italic>Brugia malayi<\/jats:italic>\n                    model of minocycline versus doxycycline. Doxycycline exhibits superior PK in comparison to minocycline resulting in a 3-fold greater exposure in SCID mice. Monte-Carlo simulations confirmed that a bi-daily 25\u201340\u2009mg\/Kg regimen is bioequivalent to a clinically effective 100\u2013200\u2009mg\/day dose for these tetracyclines. Pharmacodynamic studies showed that minocycline depletes\n                    <jats:italic>Wolbachia<\/jats:italic>\n                    more effectively than doxycycline (99.51% vs. 90.35%) after 28\u2009day 25\u2009mg\/Kg\n                    <jats:italic>bid<\/jats:italic>\n                    regimens with a more potent block in microfilarial production. PK\/PD analysis predicts that minocycline would be expected to be 1.7 fold more effective than doxycycline in man despite lower exposure in our infection models. Our findings warrant onward clinical investigations to examine the clinical efficacy of minocycline treatment regimens against lymphatic filariasis and onchocerciasis.\n                  <\/jats:p>","DOI":"10.1038\/srep23458","type":"journal-article","created":{"date-parts":[[2016,3,21]],"date-time":"2016-03-21T06:33:33Z","timestamp":1458542013000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Minocycline as a re-purposed anti-Wolbachia macrofilaricide: superiority compared with doxycycline regimens in a murine infection model of human lymphatic filariasis"],"prefix":"10.1038","volume":"6","author":[{"given":"Raman","family":"Sharma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghaith Al","family":"Jayoussi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayley E.","family":"Tyrer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Gamble","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Hayward","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana F.","family":"Guimaraes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill","family":"Davies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Waterhouse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren A. 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