Pharmacokinetics and metabolism of dietary kaempferol and its metabolite 4-hydroxy-phenylacetic acid in rats

Zabela, V. and Sampath, C. and Oufir, M. and Moradi-Afrapoli, F. and Butterweck, V. and Hamburger, M.. (2016) Pharmacokinetics and metabolism of dietary kaempferol and its metabolite 4-hydroxy-phenylacetic acid in rats. Fitoterapia, 115. pp. 189-197.

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Kaempferol is a major flavonoid in the human diet and in medicinal plants. The compound exerts anxiolytic activity when administered orally in mice, while no behavioural changes were observed upon intraperitoneal administration, or upon oral administration in gut sterilized animals. 4-Hydroxyphenylacetic acid (4-HPAA), which possesses anxiolytic effects when administered intraperitoneally, is a major intestinal metabolite of kaempferol. Pharmacokinetic properties of the compounds are currently not clear.
Methods and results
UHPLC-MS/MS methods were validated to support pharmacokinetic studies of kaempferol and 4-HPAA in rats. Non-compartmental and compartmental analyses were performed. After intravenous administration, kaempferol followed a one-compartment model, with a rapid clearance (4.40–6.44 l/h/kg) and an extremely short half-life of 2.93–3.79 min. After oral gavage it was not possible to obtain full plasma concentration–time profiles of kaempferol. Pharmacokinetics of 4-HPAA was characterized by a two-compartment model, consisting of a quick distribution phase (half-life 3.04–6.20 min) followed by a fast elimination phase (half-life 19.3–21.1 min).
Plasma exposure of kaempferol is limited by poor oral bioavailability and extensive metabolism. Both compounds are rapidly eliminated, so that effective concentrations at the site of action do not appear to be reached. At present, it is not clear how the anxiolytic-like effects reported for the compounds can be explained.
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Ehemalige Einheiten Pharmazie > Pharmazeutische Biologie (Hamburger)
UniBasel Contributors:Hamburger, Matthias and Zabela, Volha and Moradiafrapoli, Fahimeh and Oufir, Mouhssin
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:30 Oct 2017 09:19
Deposited On:30 Oct 2017 09:19

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