Determination
of Pharmacokinetics of Chrysin and Its
Conjugates in Wild-Type FVB and Bcrp1 Knockout Mice Using a Validated
LC-MS/MS Method
- Publication date
- Publisher
Abstract
Chrysin, a flavone found in many
plants, is also available as a
dietary supplement because of its reported anticancer activities.
However, its bioavailability is very poor due to extensive phase II
metabolism. The purpose of this study was to develop an UPLC-MS/MS
method to simultaneously quantify chrysin and its phase II metabolites,
and to determine its pharmacokinetics in FVB wild-type and Bcrp knockout
(Bcrp1 −/−) mice. In addition, the role of BCRP in chrysin
phase II disposition was further investigated in Caco-2 cells. The
results showed that our sensitive and reproducible UPLC-MS/MS method
was successfully applied to the pharmacokinetic study of chrysin in
wild-type and Bcrp1 (−/−) FVB mice after oral administration
(20 mg/kg). Although there was no significant change in systemic exposure
of chrysin and its metabolites, it was found that the <i>T</i><sub>max</sub> for chrysin glucuronide was significantly shorter
(<i>p</i> < 0.01) in Bcrp1-deficient mice. Furthermore,
it was shown that inhibition of BCRP by Ko143 significantly reduced
the efflux of chrysin sulfate in Caco-2 cells. In conclusion, BCRP
had significant but less than expected impact on pharmacokinetics
of chrysin and its conjugates, which were determined using a newly
developed and validated LC-MS/MS method