{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T09:51:52Z","timestamp":1791971512966,"version":"4.3.4"},"reference-count":68,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Malaria remains a persistent global health challenge, worsened by the emergence of drug\u2010resistant\n                    <jats:italic>Plasmodium<\/jats:italic>\n                    strains. This review synthesizes the pharmacokinetics (PK) and pharmacodynamics (PD) of key antimalarial agents, evaluating how these properties influence the performance of current pharmacological regimens. Findings in the literature indicate that artemisinin\u2010based combination therapies (ACTs) achieve rapid parasite clearance by using short\u2010acting artemisinin derivatives paired with longer\u2010acting partner drugs. PK\/PD modeling consistently demonstrates that well\u2010matched half\u2010lives and sustained post\u2010treatment exposure are critical to prevent functional monotherapy\u2010related resistance. Non\u2010artemisinin and triple combination regimens show promise in overcoming multidrug resistance, but gaps remain in exposure\u2013response characterization, dose alignment, and population\u2010specific optimization. A discussion of PK\/PD modeling across agents, including chloroquine, artemisinin and its derivatives, mefloquine, primaquine, and tafenoquine, highlights how inadequate drug exposure, mismatched partner drug kinetics, and host metabolic variability contribute to treatment failure. Collectively, the evidence suggests that refining combination regimens through PK\/PD\u2010guided dose optimization is crucial for maintaining efficacy and preventing resistance. Future research must prioritize host\u2010specific factors, stage\u2010specific drug activity, and optimized combination regimens to improve therapeutic outcomes and support malaria eradication.\n                  <\/jats:p>","DOI":"10.1002\/jcph.70291","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T07:37:51Z","timestamp":1789025871000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacokinetics and Pharmacodynamics of Antimalarial Agents: Optimizing Combination Therapies to Overcome Resistance Mechanisms"],"prefix":"10.1002","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-5397-3432","authenticated-orcid":false,"given":"Kiana","family":"Pica","sequence":"first","affiliation":[{"name":"Center for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, College of Pharmacy University of Florida  Orlando FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2302-8949","authenticated-orcid":false,"given":"Oliver","family":"Grundmann","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, College of Pharmacy University of Florida  Gainesville FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3625-0186","authenticated-orcid":false,"given":"Francine Johansson","family":"Azeredo","sequence":"additional","affiliation":[{"name":"Center for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, College of Pharmacy University of Florida  Orlando FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,10]]},"reference":[{"key":"e_1_2_15_2_1","unstructured":"World Health Organization.World malaria report 2025.World Health Organization. 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