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The following message was posted to: PharmPK
Dear all,
How would you test bioequivalence between two formulations of a drug
with extremely low bioavailability? Any guidance available?
Yanhong
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The following message was posted to: PharmPK
Can you be please more explicit in your question? Is it something to
do with
narrow therapeutic index (NTI)?
Naushad
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s.o.o
The reference standard you use should always be a good product
preferably the one of the original manufacturers. Idealy should be
from a competent company
It does not matter whether the drug under study is of good quality or
poor quality.
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The following message was posted to: PharmPK
Hi Naushad,
Thanks for your response.
I know there is a chapter in the FDA guidance on BA and BE with NTI.
What about a drug which just has low bioavailability (nothing to do
NTI)?
Thanks!
Yanhong
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The following message was posted to: PharmPK
Yanhong
As far as I know there is no specifics Guidelines (neither FDA nor EMEA)
for investigation on bioavaliability or bioequivalence of very low (oral
?) products. With such an issue you might consider steady state study or
single dose study with a higher dose (of course within the clinical
acceptable limits for healthy subjects), so that you can easily quantify
plasma drug concentrations in order to get a good pk profile (minimum
6-8 points). Also don't forget to look at the Vd, as it influences drug
concentration measure.
Best regards
Faculty of Pharmacy, U.L.
Biopharmaceutics and Pharmacokinetics Dept.
Av. Prof. Gama Pinto
1649 003 Lisbon / Portugal
Tel: (+351) 217 946 406
Fax: (+351) 217 937 703
E-mail: nmens.aaa.ff.ul.pt
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Dear Yanhong
If the drug has a very low bioavailability in plasma, you might look
for
other biological fluid. Like for example, alendronate has a avery low
bioavailability (<5%), the bioequivalence is determined depending on the
urine concentration.
Hope this helps.
regards
Isra' Admour, M.Sc Pharm
Regualtory Affairs Director
International Pharmaceutical Research Center (IPRC)
Tel: +962-6-5627651/52/48 (ext. 225)
PO Box 963166, Amman11196, Jordan
www.iprc.com.jo
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Dear Yanhong,
In such a case, you may try dosing two units (together) of each
treatment, so that measurable plasma concentrations are achieved.
However, it depends also on the tolerability of the molecule in healthy
volunteers.
I have seen FDA recommending such designs for products having low
bioavailability.
Anyway, it would be a better idea to discuss the protocol with the
concerned regulatory authority before going ahead.
Hope it helps.
Regards,
Hitesh K Maheshwari
Group Leader-R&D
Hikma Pharmaceuticals
Amman, Jordan
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