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This may accelerate the emergence and spread of resistance, thereby shortening the useful life of the drug, but it is an inevitable consequence of the current imprecise method of dose finding. An alternative approach to dose finding is suggested in which phase 2 studies concentrate initially on pharmacokinetic-pharmacodynamic (PK-PD) characterization and\n                    <jats:italic>in vivo<\/jats:italic>\n                    calibration of\n                    <jats:italic>in vitro<\/jats:italic>\n                    susceptibility information. PD assessment is facilitated in malaria because serial parasite densities are readily assessed by microscopy, and at low densities by quantitative PCR, so that initial therapeutic responses can be quantitated accurately. If the\n                    <jats:italic>in vivo<\/jats:italic>\n                    MIC could be characterized early in phase 2 studies, it would provide a sound basis for the choice of dose in all target populations in subsequent combination treatments. Population PK assessments in phase 2b and phase 3 studies which characterize PK differences between different age groups, clinical disease states, and human populations can then be combined with the PK-PD observations to provide a sound evidence base for dose recommendations in different target groups.\n                  <\/jats:p>","DOI":"10.1128\/aac.00287-13","type":"journal-article","created":{"date-parts":[[2013,9,4]],"date-time":"2013-09-04T00:42:13Z","timestamp":1378255333000},"page":"5792-5807","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":97,"title":["Pharmacokinetic and Pharmacodynamic Considerations in Antimalarial Dose Optimization"],"prefix":"10.1128","volume":"57","author":[{"given":"Nicholas J.","family":"White","sequence":"first","affiliation":[{"name":"Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, ThailandCentre for Tropical Medicine, Churchill Hospital, Oxford University, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","volume-title":"Guidelines for the treatment of malaria","author":"World Health Organization","year":"2010","unstructured":"World Health Organization. 2010. 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