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Dear all
What could be the possible reasons for observing decreased relative
bioavailability with increasing doses for a drug?
The drug in question is administered subcutaneously.
Any input will be highly appreciated.
Thank you
Mathangi.
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The following message was posted to: PharmPK
Dear Mathangi,
Administering higher doses (and hence volumes) at a single site would
lead
to a decrease in the ratio of surface area to volume and hence a slower
rate
of absorption from the subcutaneous site. Even though the entire dose
may
eventually be absorbed, this slower rate of absorption could lead to an
apparent lower bioavailability if blood samples are only taken for a
limited
period of time.
Ronette Gehring
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The following message was posted to: PharmPK
Probably absorption from SC tissue is decreasing with the increased
concentration .
S. Eralp Bellibas, MD.
Associate Clinical Director
Hoffmann-La Roche Inc.
Global Drug Development
Department of Clinical Pharmacology
340 Kingsland St.
Nutley, NJ USA 07110
Tel. +1 (973) 235-2411
Fax +1 (973) 235-5635
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The following message was posted to: PharmPK
Mathangi,
One possible reason may be that your compound has a high clearance.
This would mean that at lower doses the compound is being cleared faster
than it is being absorbed hence a lower apparent bioavailability than at
higher doses. Do you have any i.v. data for the compound?
Nick Kerwin
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The following message was posted to: PharmPK
Poor formulation go back to the drawing board. Check all the Excipients
you have used. Secondly Check the equipment you have used in making
your drug
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