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Please post the following question:
Does anyone have information regarding the PK of multiple doses of Donepezil in the Rat. Specifically, if there are difference between oral gavage and medicated feed administration. Efraim Shek, Ph.D.
Executive Vice President, Research & Development
Adamas Pharmaceuticals, Inc. 1900 Powell St., Suite 1050
Emeryville, CA 94608
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Dear Efraim,
Despite no effect of food seen in clinical studies, administration of donepezil with food dramatically lowers its bioavailability in rats. I think bioavailability decreases by something like 85% when administered with food compared to fasting in rats. This is consistently observed in the dose range 1 to 10 mg/kg. Does this help?
Cheers,
Dave
Dr David Critchley
Executive Director, Clinical Pharmacology & Translational Medicine
Scientific and Operational Clinical Support Core Function Unit
Eisai Product Creation Systems
European Knowledge Centre
Mosquito Way
Hatfield
Herts
AL10 9SN
United Kingdom
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The following message was posted to: PharmPK
Dear David,
Thanks for the information. I am still puzzled since reported data indicate that to achieve required exposure level in the rat one should administered Donepezil in medicated feed rather than by gavage? Any explanation to that?
ef
Efraim Shek, Ph.D.
Executive Vice President, Research & Development
Adamas Pharmaceuticals, Inc. 1900 Powell St., Suite 1050
Emeryville, CA 94608
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