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However, the mechanism of action and overall impact on malaria transmission is still unknown. Using data from 81 adult Malians with <jats:italic>P<\/jats:italic>.\u00a0<jats:italic>falciparum<\/jats:italic> gametocytemia who received the standard dihydroartemisinin\u2010piperaquine treatment course and were randomized to receive either a single dose of primaquine between 0.0625 and 0.5\u00a0mg base\/kg or placebo, we characterized the pharmacokinetic\u2010pharmacodynamic relationships for transmission blocking activity. Both gametocyte clearance and mosquito infectivity were assessed. A mechanistically linked pharmacokinetic\u2010pharmacodynamic model adequately described primaquine and carboxy\u2010primaquine pharmacokinetics, gametocyte dynamics, and mosquito infectivity at different clinical doses of primaquine. Primaquine showed a dose\u2010dependent gametocytocidal effect that precedes clearance. A single low dose of primaquine (0.25\u00a0mg\/kg) rapidly prevented <jats:italic>P.\u00a0falciparum<\/jats:italic> transmissibility.<\/jats:p>","DOI":"10.1002\/cpt.2512","type":"journal-article","created":{"date-parts":[[2021,12,14]],"date-time":"2021-12-14T14:33:22Z","timestamp":1639492402000},"page":"676-685","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Mechanistic Modeling of Primaquine Pharmacokinetics, Gametocytocidal Activity, and Mosquito Infectivity"],"prefix":"10.1111","volume":"111","author":[{"given":"Palang","family":"Chotsiri","sequence":"first","affiliation":[{"name":"Mahidol\u2010Oxford Tropical Medicine Research Unit Faculty of Tropical Medicine Mahidol University Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Almahamoudou","family":"Mahamar","sequence":"additional","affiliation":[{"name":"Malaria Research and Training Centre Faculty of Pharmacy and Faculty of 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