{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T05:13:00Z","timestamp":1788671580972,"version":"build-2803163510"},"reference-count":42,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"State of Nebraska"},{"name":"Pediatric Cancer Research Group"},{"DOI":"10.13039\/100018789","name":"Child Health Research Institute","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100018789","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Team Jack Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Artesunate (ART) is an FDA-approved antimalarial drug and is currently being repurposed for various solid tumor treatments. However, there are no safety or pharmacokinetic (PK) studies in mice exploring its potential application in murine brain tumor models. This study aims to delineate the tolerability and PK of ART in healthy NOD scid gamma (NSG) mice to inform future efficacy studies. The maximum tolerated dose (MTD) of ART following intraperitoneal (IP) administration was determined by a single-dose escalation method. PK and brain penetration of ART and its active metabolite, dihydroartemisinin (DHA), were analyzed using an optimized LC-MS\/MS bioanalytical method, following single oral and IP doses (100 mg\/kg). A 350 mg\/kg IP dose was well tolerated with no evidence of systemic and organ-specific toxicities. Bioanalytical assay results were linear (R2 &gt; 0.99) over a range of 5\u20131000 ng\/mL. An optimized extraction method employing low sample volume improved analyte recovery from brain homogenate by 2-fold. PK studies showed rapid absorption with short elimination half-lives (t1\/2: 8\u201322 min) and higher systemic and brain exposure for ART and DHA following IP administration over oral dosing. We conclude that ART is well-tolerated at high doses (350 mg\/kg, IP) in NSG mice, although repeated doses may be necessary for therapeutic efficacy in brain tumors given its rapid elimination kinetics.<\/jats:p>","DOI":"10.3390\/molecules31173111","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T16:07:32Z","timestamp":1788538052000},"page":"3111","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacokinetics and Toxicity Assessment of Artesunate and Its Metabolite, Dihydroartemisinin, in NOD Scid Gamma Mice"],"prefix":"10.3390","volume":"31","author":[{"given":"Prachi","family":"Agrawal","sequence":"first","affiliation":[{"name":"Clinical Pharmacology Laboratory, Department of Pharmacy Practice and Science, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7790-2350","authenticated-orcid":false,"given":"Sandeep K.","family":"Singh","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Laboratory, Department of Pharmacy Practice and Science, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4841-286X","authenticated-orcid":false,"given":"Geoffrey","family":"Talmon","sequence":"additional","affiliation":[{"name":"Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 69198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2483-0610","authenticated-orcid":false,"given":"Sidharth","family":"Mahapatra","sequence":"additional","affiliation":[{"name":"Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 69198, USA"},{"name":"Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA"},{"name":"Department of Pediatrics, Children\u2019s Nebraska, University of Nebraska Medical Center, Omaha, NE 69198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4169-5027","authenticated-orcid":false,"given":"Daryl J.","family":"Murry","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Laboratory, Department of Pharmacy Practice and Science, University of Nebraska Medical Center, Omaha, NE 68198, USA"},{"name":"Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 69198, USA"},{"name":"Department of Pediatrics, Children\u2019s Nebraska, University of Nebraska Medical Center, Omaha, NE 69198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1007\/s00706-021-02759-x","article-title":"Antimalarial and anticancer properties of artesunate and other artemisinins: Current development","volume":"152","author":"Khanal","year":"2021","journal-title":"Monatsh. 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