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- W4220678752 abstract "Regorafenib is glucuronidated mainly by uridine 5'-diphosphate glucuronosyltransferase (UGT) 1A9 in humans. UGT1A9 and its orthologues are expressed in the liver, small intestine, and kidney in humans and laboratory animals. The aim of this study was to reveal the species and tissue differences in regorafenib glucuronidation in the liver and extrahepatic tissues of humans and laboratory animals.Regorafenib glucuronidation was fitted to the Michaelis-Menten model in humans, monkeys, and mice using liver, kidney, and small intestine tissue. The hepatic results indicated monophasic kinetics in all species except rats, in which glucuronide could not be detected because rat Ugt1a9 is a pseudogene.The maximum velocity was higher in monkeys (3.41 pmol/min/mg) than in humans (1.21 pmol/min/mg), but was similar between humans and mice (1.11 pmol/min/mg). The maximum velocity in the kidney was higher than that in the liver in both humans and monkeys. Regorafenib glucuronide was not quantified in the kidneys of mice. Small intestinal regorafenib glucuronidation was not detected in any of the species. It is surmised that the degree of regorafenib glucuronidation is dependent on UGT1A9 expression levels.Our study clarified the species and tissue differences in regorafenib glucuronidation in the liver and extrahepatic tissues." @default.
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- W4220678752 date "2022-02-01" @default.
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- W4220678752 title "Species and tissue differences in regorafenib glucuronidation" @default.
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- W4220678752 doi "https://doi.org/10.1080/00498254.2022.2055507" @default.
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