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This concerns the bioavailability of a IM formulation. I have come across
data in which IM F is over 150% of IV . While i am aware that
overestimation occurs in some cases, i need to know other reasons involved
in getting such large bioavailability values for extravascular
administration and or Non IV administration.
kindly enlighten me more on this, anybody ?
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[A few replies -db]
Reply-To: "Stephen Duffull"
From: "Stephen Duffull"
To:
Subject: Re: PharmPK Overestimation of AUC
Date: Tue, 23 Mar 1999 09:13:17 -0000
MIME-Version: 1.0
X-Priority: 3
I can think of three reasons why extravascular
administration of a drug may have a greater F:
1) The IV drug may be given as a salt.
2) Loss of drug into the intravenous giving set.
3) Non linear PK (if the drug is administered by slow IVI)
Hope this helps
Regards
Steve
=====================
Stephen Duffull
School of Pharmacy
University of Manchester
Manchester, M13 9PL, UK
Ph +44 161 275 2355
Fax +44 161 275 2396
---
From: "Sasso, Patrick [PRI]"
To: "'PharmPK.at.pharm.cpb.uokhsc.edu'"
Subject: RE: PharmPK Overestimation of AUC
Date: Tue, 23 Mar 1999 08:52:06 -0500
MIME-Version: 1.0
Was the dose given properly ??? IM can accidentally become IV if
administered poorly !!
Also, at high dosing levels, (say ten times therapeutic) the correction for
dose won't suffice (you would also have to dose the IV at ten times
therapeutic, and even this might not be enough).
---
Date: Tue, 23 Mar 1999 08:53:29 -0700
From: "David Nix, Pharm D."
Organization: College of Pharmacy
MIME-Version: 1.0
To: PharmPK.-a-.pharm.cpb.uokhsc.edu
Subject: Re: PharmPK Overestimation of AUC
You may want to consider all steps that are involved in the IV
administration. Many times, some of the drug is lost to the
adminisration apparatus and is never delivered. It would be helpful to
set up the dose and administration apparatus and do in-vitro experiments
to determine the actual drug delivery through the iv catheter. If drug
is lost you can isolate the specific cause in subsequent experiments.
Are you using extrapolated AUC for bioavailability assessment? Is the
half-life of the IM administered drug longer than the IV administered
drug? If so, there may be artifact due to the sampling schedule and/or
inability to estimate the true elimination rate. The higher that
AUC(t*-inf) is compared to AUC(0-inf) the more likely that this could
introduce artifact.
David Nix
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Hi,
I had a similar experience with an im formulation in oil. The conclusion
we came to was that prolonged and variable absorption of the drug from the
im injection site resulted in inaccurate parameter estimates of elimination
during data analysis. This resulted in inflated AUCs. We confirmed this
using deconvolution. I have heard that other factors such as lymphatic
uptake can contribute to unrealistically large AUCs following im
administration too.
Hope this helps.
Regards,
Jim Peggins
**************************
James O. Peggins, Ph.D.
Food & Drug Administration
Center for Veterinary Medicine
Division of Residue Chemistry
8401 Muirkirk Rd
Laurel, MD 20708
Voice: (301) 827-8092
Fax: (301) 827-8170
***************************
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> I had a similar experience with an im formulation in oil. The conclusion
> we came to was that prolonged and variable absorption of the drug from the
> im injection site resulted in inaccurate parameter estimates of elimination
> during data analysis. This resulted in inflated AUCs. We confirmed this
> using deconvolution.
Could you be more specific about this analysis and results
or give us a reference citation?
Best regards,
Maria Durisova
Institute of Experimental Pharmacology
Slovak Academy of Sciences
SK-842 16 Bratislava
Phone/Fax: 00421 7 5477 5928
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