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Human plasma metabolic profiles of benzydamine, a flavin-containing monooxygenase probe substrate, simulated with pharmacokinetic data from control and humanized-liver mice.
- Source :
- Xenobiotica; Feb2018, Vol. 48 Issue 2, p117-123, 7p
- Publication Year :
- 2018
-
Abstract
- 1. Benzydamine is used clinically as a nonsteroidal anti-inflammatory drug in oral rinses and is employed in preclinical research as a flavin-containing monooxygenase (FMO) probe substrate. In this study, plasma concentrations of benzydamine and its primaryN-oxide andN-demethylated metabolites were investigated in control TK-NOG mice, in humanized-liver mice, and in mice whose liver cells had been ablated with ganciclovir. 2. Following oral administration of benzydamine (10 mg/kg) in humanized-liver TK-NOG mice, plasma concentrations of benzydamineN-oxide were slightly higher than those of demethyl benzydamine. In contrast, in control and ganciclovir-treated TK-NOG mice, concentrations of demethyl benzydamine were slightly higher than those of benzydamineN-oxide. 3. Simulations of human plasma concentrations of benzydamine and itsN-oxide were achieved using simplified physiologically based pharmacokinetic models based on data from control TK-NOG mice and from reported benzydamine concentrations after low-dose administration in humans. Estimated clearance rates based on data from humanized-liver and ganciclovir-treated TK-NOG mice were two orders magnitude high. 4. The pharmacokinetic profiles of benzydamine were different for control and humanized-liver TK-NOG mice. Humanized-liver mice are generally accepted human models; however, drug oxidation in mouse kidney might need to be considered when probe substrates undergo FMO-dependent drug oxidation in mouse liver and kidney. [ABSTRACT FROM PUBLISHER]
- Subjects :
- MONOOXYGENASES
PHARMACOKINETICS
BLOOD plasma
OXIDATION
LABORATORY mice
FLAVINS
Subjects
Details
- Language :
- English
- ISSN :
- 00498254
- Volume :
- 48
- Issue :
- 2
- Database :
- Complementary Index
- Journal :
- Xenobiotica
- Publication Type :
- Academic Journal
- Accession number :
- 126917399
- Full Text :
- https://doi.org/10.1080/00498254.2017.1288280