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Occasionally, we find in PK studies clearance and volume of distribution
expressed as a function of bioavailability (CL/F, V/F). Can anyone provide
a rational for using these terms or a reference defining their use?
Thanks,
Mike
Mike Jones, Pharm.D.
mike.jones.-at-.mdx.com
Micromedex / Thomson Healthcare
6200 S. Syracuse Way #300
Greenwood Village, CO 80111-4740
(303) 486-6723
1-800-525-9083 ext. 6723
www.micromedex.com/mlm.htm
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=46rom: "Stephan, Thomas"
Date: Tue, 2 Oct 2001 13:36:52 -0700
To: david.-at-.boomer.org
Subject: RE: PharmPK
Status: R
The following message was posted to: PharmPK
Greetings Mike...
Clearance and volume of distribution parameters are calculated
dependent on the amount of compound that actually enters the circulation.
If you do not take into consideration the bioavailability term in your
calculations you are assuming 100% bioavailability. This may be ok for iv
administration where all compound dosed enters the circulation, however for
other routes (oral, sc, etc.) where there is an absorption that must take
place, the bioavailability of the compound from that route needs to be
considered because it is possible that not all the compound dosed enters the
circulation. If you do not take into consideration the bioavailability it
is possible that you will overestimate the clearance and volume of
distribution parameters. Hope this helps!!
Tom Stephan, Ph.D.
ICOS Corporation
tstephan.-at-.icos.com
---
From: Serge Guzy
Date: Tue, 2 Oct 2001 14:31:53 -0700
To: david.-at-.boomer.org
Subject: RE: PharmPK Definitions: CL/F and V/F
Status: R
The following message was posted to: PharmPK
One of the reasons is for oral experiments where you cannot fit observed
data to (for example) a 1 compt model and obtaining both V and F. The 2
paramters are not identifiable but only their ratio. The ratio appears
naturally when writing a mass balance for the state variables.
Serge Guzy
Head of Pharmacometrics
Xoma
---
From: Thomas.Senderovitz.aaa.ferring.com
To: PharmPK.at.boomer.org
Subject: RE: PharmPK Definitions: CL/F and V/F
Date: Wed, 3 Oct 2001 08:05:54 +0200
MIME-Version: 1.0
Mike,
These termes refer to the fact that the parameters are derived from
studies in which the drug was not dosed intravenously. As a
consequence, you can only estimate CL and V relative to the
bioavailability.
Regards,
Thomas Senderovitz, M.D.
Director Clinical Pharmacology & Kinetics
=46erring Pharmaceuticals A/S
International Center
Borups All=E9 177D
DK-2400 Copenhagen NV
DENMARK
Phone (direct) +45 38 15 04 58
Switchboard +45 38 15 03 00
Mobile phone: +45 24 25 52 24
=46ax: +45 38 15 03 05
E-mail: thomas.senderovitz.aaa.ferring.com
Web: www.ferring.com
---
=46rom: "Bruce CHARLES"
Date: Wed, 3 Oct 2001 07:51:54 10
To: david.-at-.boomer.org
Subject: Re: PharmPK Definitions: CL/F and V/F +++REPLY+++
Status: R
The following message was posted to: PharmPK
Send reply to: PharmPK.-at-.boomer.org
Date sent: Tue, 2 Oct 2001 14:41:16 -0500
From: "Jones, Mike"(by way of David_Bourne=
)
To: Multiple recipients of PharmPK - Sent by>
Subject: PharmPK Definitions: CL/F and V/F
Because one implicity assumes 100% of administered dose is
available to the biololgy (filtration and metabolism for CL,
tissue binding for V).
If dose is extravascular where F is usually <1, then failure to correct
CL and V for F will give overestimation of CL and V. If the F value is
known or assumed (e.g. no i.v. data) then can easily correct CL and
V for this value to give the "true" CL and V. Otherwise, CL/F and
V/F become "hybrid" parameters whose respective values depend
on whatever the (unknown) F value is for that drug in that biological
system.
Cheers,
BC
Bruce CHARLES
BPharm(Hons), GradDipBusAdmin, PhD, MPS
Associate Professor
Director, The Australian Centre for Paediatric Pharmacokinetics
University of Queensland, School of Pharmacy, QLD 4072
Australia
+61 7 336 53194 (TEL)
+61 7 336 51688 (FAX)
0403 022 252 (MOBILE)
b.charles.-a-.pharmacy.uq.edu.au
http://www.uq.edu.au/pharmacy/charles.html
http://www.mater.org.au/pharm/accp/index.htm
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