POSTER PRESENTATION ABSTRACTS
Please note: All posters will be displayed in
Salons 10-12.
FRIDAY, 10:15-11:00 AM
Shia CS, Hsiu SL, Wen KC.
A comparative study on dose-dependent interactions of
morin and quercetin with cyclosporine in rats.
School of Cosmeceutic, China Medical University
kcwen520@mail.cmu.edu.tw
PURPOSE: Cyclosporin, an immunosuppressant with
narrow therapeutic window, is a substrate for both CYP3A4 and P-glycoprotein
(Pgp). Morin is a constitutional isomer of quercetin, an inhibitor of
CYP3A4 and Pgp. Our previous studies indicated that morin exhibited
nonlinear pharmacokinetics in rats and rabbits. Therefore, this study
aimed to measure the effects of various doses of morin and quercetin
on the absorption and disposition of cyclosporin in rats.
METHODS: Cyclosporin (Neoral¨, 2.5 mg/kg) was
orally administered with and without concomitant doses of morin (50.0,
37.5 and 25.0 mg/kg) or quercetin (50.0 and 20.0 mg/kg) to rats, respectively.
Blood samples were withdrawn via cardiopuncture at predetermined time
points and cyclosporin blood concentrations were determined by a specific
monoclonal fluorescence polarization immunoassay.
RESULTS: The coadministration of 50.0 mg/kg
morin significantly decreased AUC0-t of cyclosporine by 78 % and significantly
lowered the MRT (mean residence time) by 62%, whereas 37.5 mg/kg morin
did not show significant influence. However, the coadministration of
25.0 mg/kg morin significantly increased the Cmax and AUC0-t of cyclosporine
by 114 and 149%, In contrast, both doses of 50.0 and 20.0 mg/kg quercetin
significantly decreased the Cmax and AUC0-t of cyclosporin.
CONCLUSION: In conclusion, quercetin markedly
decreased the oral bioavailability of cyclosporine irrespective of dose,
whereas the influence of morin was dose dependent.
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