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- W2037673903 abstract "Abstract Objectives This study focuses on the in-vitro metabolic profiles of pentamethyl-chromanol in human, rat, dog and non-human primates, and characterizes the associated metabolic kinetics and specific human isozymes responsible for metabolism. Additional investigations compare in-vitro data with in-vivo metabolic data from rats and dogs. Methods In-vitro metabolites were generated from commercially available microsomes, S9 fractions and cytochrome P450 isozymes. Reaction mixtures were analysed using liquid chromatography/tandem mass spectrometry for metabolite identification, stability, pheno-typing and kinetic profiles. Plasma samples were collected from 28-day toxicology studies in rats and dogs, and analysed using the same methodology as for the identification of in-vitro metabolites. Key findings Samples from in-vitro experiments produced a total of eight identified metabolites while five were observed in the in-vivo samples. Kinetic analysis of metabolites in human microsomes generated Michaelis constants (KM) ranging from 10.9 to 104.9 μM. Pentamethylchromanol metabolic stability varied by species and multiple isozymes were identified for the observed biotransformation pathways. Pentamethylchromanol is susceptible to multiple metabolic pathways and differential metabolic stability, which is species dependent. Conclusions In-vitro metabolism was not a strong predictor of in-vivo metabolism for the samples assays but showed glucuronidation and sulfation as common biotransformation pathways." @default.
- W2037673903 created "2016-06-24" @default.
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- W2037673903 date "2009-10-01" @default.
- W2037673903 modified "2023-09-23" @default.
- W2037673903 title "In-vitro and in-vivo metabolic studies of the candidate chemopreventative pentamethylchromanol using liquid chromatography/tandem mass spectrometry" @default.
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- W2037673903 doi "https://doi.org/10.1211/jpp.61.10.0006" @default.
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