Pharmacokinetic characterization of supinoxin and its physiologically based pharmacokinetic modeling in rats

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dc.contributor.authorYoo-Kyung Song-
dc.contributor.authorY H Seol-
dc.contributor.authorMin Ju Kim-
dc.contributor.authorJong Woo Jeong-
dc.contributor.authorH I Choi-
dc.contributor.authorS W Lee-
dc.contributor.authorY J Chae-
dc.contributor.authorS Ahn-
dc.contributor.authorY D Gong-
dc.contributor.authorKyeong-Ryoon Lee-
dc.contributor.authorT S Koo-
dc.date.accessioned2021-04-06T03:30:56Z-
dc.date.available2021-04-06T03:30:56Z-
dc.date.issued2021-
dc.identifier.issn1999-4923-
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/24241-
dc.description.abstractSupinoxin is a novel anticancer drug candidate targeting the Y593 phospho-p68 RNA helicase, by exhibiting antiproliferative activity and/or suppression of tumor growth. This study aimed to characterize the in vitro and in vivo pharmacokinetics of supinoxin and attempt physiologically based pharmacokinetic (PBPK) modeling in rats. Supinoxin has good permeability, comparable to that of metoprolol (high permeability compound) in Caco-2 cells, with negligible net absorptive or secretory transport observed. After an intravenous injection at a dose range of 0.5-5 mg/kg, the terminal half-life (i.e., 2.54-2.80 h), systemic clearance (i.e., 691-865 mL/h/kg), and steady state volume of distribution (i.e., 2040-3500 mL/kg) of supinoxin remained unchanged, suggesting dose-independent (i.e., dose-proportional) pharmacokinetics for the dose ranges studied. After oral administration, supinoxin showed modest absorption with an absolute oral bioavailability of 56.9-57.4%. The fecal recovery following intravenous and oral administration was 16.5% and 46.8%, respectively, whereas the urinary recoveries in both administration routes were negligible. Supinoxin was mainly eliminated via NADPH-dependent phase I metabolism (i.e., 58.5% of total clearance), while UDPGA-dependent phase II metabolism appeared negligible in the rat liver microsome. Supinoxin was most abundantly distributed in the adipose tissue, gut, and liver among the nine major tissues studied (i.e., the brain, liver, kidneys, heart, lungs, spleen, gut, muscles, and adipose tissue), and the tissue exposure profiles of supinoxin were well predicted with physiologically based pharmacokinetics.-
dc.publisherMDPI-
dc.titlePharmacokinetic characterization of supinoxin and its physiologically based pharmacokinetic modeling in rats-
dc.title.alternativePharmacokinetic characterization of supinoxin and its physiologically based pharmacokinetic modeling in rats-
dc.typeArticle-
dc.citation.titlePharmaceutics-
dc.citation.number3-
dc.citation.endPage373-
dc.citation.startPage373-
dc.citation.volume13-
dc.contributor.affiliatedAuthorYoo-Kyung Song-
dc.contributor.affiliatedAuthorMin Ju Kim-
dc.contributor.affiliatedAuthorJong Woo Jeong-
dc.contributor.affiliatedAuthorKyeong-Ryoon Lee-
dc.contributor.alternativeName송유경-
dc.contributor.alternativeName설윤환-
dc.contributor.alternativeName김민주-
dc.contributor.alternativeName정종우-
dc.contributor.alternativeName최해인-
dc.contributor.alternativeName이승원-
dc.contributor.alternativeName채윤지-
dc.contributor.alternativeName안선주-
dc.contributor.alternativeName공영대-
dc.contributor.alternativeName이경륜-
dc.contributor.alternativeName구태성-
dc.identifier.bibliographicCitationPharmaceutics, vol. 13, no. 3, pp. 373-373-
dc.identifier.doi10.3390/pharmaceutics13030373-
dc.subject.keywordPhosphorylated p68-
dc.subject.keywordSupinoxin-
dc.subject.keywordPharmacokinetics-
dc.subject.keywordPhysiologically based pharmacokinetic modeling-
dc.subject.localPhosphorylated p68-
dc.subject.localSupinoxin-
dc.subject.localpharmacokinetics-
dc.subject.localPharmacokinetics-
dc.subject.localPhysiologically based pharmacokinetic modeling-
dc.description.journalClassY-
Appears in Collections:
Ochang Branch Institute > Division of National Bio-Infrastructure > Laboratory Animal Resource & Research Center > 1. Journal Articles
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