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

Cited 0 time in scopus
Metadata Downloads
Title
Pharmacokinetic characterization of supinoxin and its physiologically based pharmacokinetic modeling in rats
Author(s)
Yoo-Kyung Song; Y H Seol; Min Ju Kim; Jong Woo Jeong; H I Choi; S W Lee; Y J Chae; S Ahn; Y D Gong; Kyeong-Ryoon Lee; T S Koo
Bibliographic Citation
Pharmaceutics, vol. 13, no. 3, pp. 373-373
Publication Year
2021
Abstract
Supinoxin 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.
Keyword
Phosphorylated p68SupinoxinPharmacokineticsPhysiologically based pharmacokinetic modeling
ISSN
1999-4923
Publisher
MDPI
DOI
http://dx.doi.org/10.3390/pharmaceutics13030373
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of National Bio-Infrastructure > Laboratory Animal Resource & Research Center > 1. Journal Articles
Files in This Item:
  • There are no files associated with this item.


Items in OpenAccess@KRIBB are protected by copyright, with all rights reserved, unless otherwise indicated.