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Dear Colleagues,
I would like to know if any one has information about differences in
the plasma protein binding of acidic compounds between in vitro and
in vivo.
I found a PB of 91.7% at a concentration of 98.2 ug/mL after i.v.
injection in mouse whereas in vitro, at a concentration of 100 ug/mL,
I got a PB of 98.2%. The ultrafiltration PB method was used.
Thanks
Marco Mosca
Preclinical Pharmacology "in vivo" laboratory,
Preclinical Pharmacokinetic Unit,
Dompe S.p.A.
Via Campo di Pile, 67100 L'Aquila, Italy
Tel. ++39 0862 338388
Fax. ++39 0862 338219
E-mail: marco.mosca.-a-.dompe.it
[I wonder how different the two numbers are? Can you check the errors
in collection and analysis. Also, in vivo there may be competing
material in the blood, e.g. including metabolites that might displace
the drug - db]
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Dear Marco,
Metabolites and iv formulation ingredients could influence your PB. Try
early and late time points and compare the iv and oral route.
Best regards
Thomas
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The following message was posted to: PharmPK
Dear Marco,
Is the plasma used for "in vitro" PB studies from the same lot of
animals used for "in vivo" PB studies? Is it freshly collected?
In addition to what db pointed out, the difference could also be due to
the variation in the protein content as such in the two lots of plasma.
Good luck,
Kasiram.
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Did you check the pH of the plasma. It should be about 7.4 , if not
not can cause a large difference in the protein binding.
Stanley Cotler
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