- On 21 Mar 2002 at 18:50:35, "Birger Brodin" (bbr.-at-.dfh.dk) sent the message

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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 - On 21 Mar 2002 at 22:28:59, "Tim Cacek, Pharm.D." (ADME.-a-.trib.net) sent the message

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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] - On 22 Mar 2002 at 10:52:39, David Bourne (david.at.boomer.org) sent the message

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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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