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Hi,
Can we submit only active metabolite data as Bioequivalence Pharmacokinetics
criteria, if the parent drug is inactive prodrug for EU submission?
Narasimha
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The following message was posted to: PharmPK
Great Question!!! I'm guessing you need to prove safety on both, but
interesting to think about!!
Matthew J. Miller, BS, LATG
Research Scientist, Metabolism
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Dear Narasimha,
we can submit only active metabolite data, if the inactive prodrug is difficult
to be measured (some pro-drugs may have low plasma concentrations and be quickly
eliminated resulting in difficulties in demonstrating bioequivalence for parent
compound), however as per ema, for inactive prodrugs also demonstrationon of
bioequivalence for parent compound is recommended.
Thanks and Regards
Santosh Kumar Manthri
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Dear Narashima-
I have worked on successful prodrugs (e.g., Valcyte, CellCept) and for those two it would
be very difficult to show bioequivalence of the parent, particularly for Valcyte, which
was believed to be cleaved to the active ganciclovir to a large extent during the
absorption process. Plasma/blood levels of both prodrugs were very low to non-detectable
in comparison to parent drug, and not very stable in the collected blood and plasma
sample.
Perhaps you can approach the authorities in advance of the study with your plan for
demonstrating bioequivalence and justification.
Tom
Thomas L. Tarnowski, Ph.D.
Corporate Liaison & Special Tasks Director
Organizing Committee
CACO Pharmaceutical and BioScience Society
ttarnowski1.at.aol.com
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