{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:08:29Z","timestamp":1792789709124,"version":"4.5.0"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,5,24]],"date-time":"2025-05-24T00:00:00Z","timestamp":1748044800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education, Youth, and Sports of the Czech Republic","award":["00179906"],"award-info":[{"award-number":["00179906"]}]},{"DOI":"10.13039\/100018512","name":"University of Hradec Kr\u00e1lov\u00e9","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018512","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Charles Universit"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>A detailed understanding of alterations in olanzapine pharmacokinetics during acute inflammatory states, associated with infections, remains lacking. This study aimed to investigate the impact of endotoxemia on the pharmacokinetics of olanzapine and desmethylolanzapine (DMO) in mice.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>C57BL\/6N mice received an intraperitoneal injection of lipopolysaccharide (LPS, 5\u00a0mg\/kg) or saline (controls), followed 24 hours later by single oral or intravenous doses of olanzapine or intravenous DMO. Concentrations and unbound fractions of olanzapine and DMO were measured in the plasma and brain homogenates.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In LPS-injected mice, the area under the concentration\u2013time curve (AUCs) for olanzapine increased 3.8-fold in the plasma and 5.2-fold in brain homogenates, in consequence of a higher absolute bioavailability of olanzapine (+200%), a lower plasma clearance (\u221234%), and a higher brain penetration ratio for the unbound drug relative to controls (Kp,uu,brain 6.2 vs. 4.1). LPS attenuated the hepatic mRNA expression of cytochrome P450 1A2 and the metabolism of olanzapine to DMO. However, the AUC of plasma DMO increased by 140% due to a 4.8-fold decrease in the plasma clearance of DMO. The brain penetration of DMO was minimal (Kp,uu,brain\u2005\u2264\u20050.051). The LPS-injected mice exhibited a downregulation of the hepatic and ileal mRNA expression of P-glycoprotein (Abcb1a), whereas the expression of Abcb1a and Abcb1b in the brain was upregulated.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Endotoxemia notably increases olanzapine concentrations in the plasma and brain following oral administration in mice. Further studies should clarify whether altered pharmacokinetics results in adverse effects in acutely infected patients taking oral olanzapine.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ijnp\/pyaf036","type":"journal-article","created":{"date-parts":[[2025,5,24]],"date-time":"2025-05-24T17:54:20Z","timestamp":1748109260000},"source":"Crossref","is-referenced-by-count":4,"title":["Acute inflammation induced by the <i>Escherichia coli<\/i> lipopolysaccharide considerably increases the systemic and brain exposure of olanzapine after oral administration in mice"],"prefix":"10.1093","volume":"28","author":[{"given":"Jan","family":"Hube\u0148\u00e1k","sequence":"first","affiliation":[{"name":"Department of Psychiatry, University Hospital and the Faculty of Medicine, Charles University , Hradec Kralove ,","place":["Czech 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