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Dear list,
a beginners question;
can absorption data somehow be extracted from knowledge just of a plasma
concentration profile after a single oral dose, without knowledge of
i.v.-data, Fa etc..? Assuming simple first order kinetics i have calculated
elimination and absortion rate constants, and would like to make an IVIV
correlation with in vitro dissolution data.
Best regards
Birger
Birger Brodin
Associate Res Prof.
RDSP, Copenhagen
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your last sentence confused me somewhat, but yes you can determine the
absorption rate constant...see the method of residuals in gibaldi.
[but you would need to assume kel > ka or vice versa or a common or
similar kel - db]
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[Two replies - db]
From: "David S. Farrier"
Date: Thu, 21 Mar 2002 22:01:15 -0700
To: david.-at-.boomer.org
Subject: Re: PharmPK Absorption rate determination
Dear Birger,
Questions such as yours can often be answered by a quick look at an
appropriate equation that would remind you of the variables needed
for solving various pharmacokinetic parameters.
You are invited to download a free listing of some 75 pharmacokinetic
equations, which will hopefully serve as a handy reference to a
variety of common, mostly non-compartmental pharmacokinetic
parameters. Our site address is:
http://www.SummitPK.com/equations/equations.htm
The download page will give you a couple of options for the format of
these equations (e.g., Word, or PDF file).
I hope this proves useful.
Kind Regards,
David
David S. Farrier, Ph.D.
Summit Research Services
68911 Open Field Dr. Email: DFarrier.-at-.SummitPK.com
Montrose, CO 81401 Web: http://www.SummitPK.com
---
From: "Birger Brodin"
Date: Fri, 22 Mar 2002 12:05:29 +0100
To: david.aaa.boomer.org
Subject: Re: PharmPK Re: Absorption rate determination
Sorry for my confusing question, it was rather late here in DK :)
The "real" question is;
having only blood plasma data following an oral dose (120 mg diltiazem from
an extended release tablet formulation) I have estimated AUC total,
k(elimination) and k(absorption)assuming simple first order eliminination
and absorption (which is not necessarily true, but..). Since I don't have
i.v. data , I don't know the volume of distribution (Vd) and fraction
absorbed (F). I then would like to make a level A correlation (USP <1088>)
between amount absorbed in vivo at given time intervals (from the plasma
data) and the amount released in vitro at the same time intervals (data from
a simple dissolution experiment). I cannot calculate the absolute values
absorbed, I suppose, but a plot of relative absorption versus time would be
OK.
And here comes the question; If I use the absorption constant calculated and
plot the time curve for absortion of an arbitrary amount of compound as a
function of time, wouldn´t this give me the shape of the absorption curve
alone? And, if so, will these data for absorption plotted agaisnt the
dissolution data fullfill the criteria for a level A correlation ? (since
I'm actually only using one parameter obtained from the plasma curve and not
performing a true point to point correlation)?
Cheers Birger
Birger Brodin, Assoc. Res. Prof.
RDSP, Copenhagen, Denmark
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)