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Hi everybody,
Does anyone know how to design a bioavailability study in humans for
an endogenous polyunsaturated fatty acid (a metabolite of the
essential fatty acid, linoleic acid) which its oral therapeutic dose
is high (1-2 grams daily) and taking into consideration that the
fatty acid will be converted in the enterocytes to triacylglycerol
form and excreted into the lymph as a chylomicron.
Labelled fatty acid may not work because the fatty acid will be
incorporated in tissues!!!!!!!.
so How can I calculate the AUC, peak conc and peak time for the fatty
acid???
Thank you
Abedel-nasser G. Abulrob BSc MSc
1st year PhD
Department of Pharmaceutics
Welsh school of Pharmacy
University of Wales/Cardiff
Cardiff CF1 3XF
e-mail: AbulrobAN.-a-.cf.ac.uk
&
abedelnasser.-at-.hotmail.com
tel (home) 01222 331 913
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From: Marksale
Date: Wed, 14 Jan 1998 15:07:49 EST
To: PharmPK.-at-.pharm.cpb.uokhsc.edu
Subject: Re: PharmPK Fatty acid pharmacokinetics
Organization: AOL (http://www.aol.com)
Dear Abedel-nasser ,
You might learn something from the experience of bio-equivalence in L-
thyroxine, very simular, with endogenous production and metabolic
transformation. The person I know who was involved with this was Darrell
Abernethy at Georgetown.
Mark
---
X-Sender: jelliffe.-a-.hsc.usc.edu
Date: Wed, 14 Jan 1998 13:26:07 -0800
To: PharmPK.aaa.pharm.cpb.uokhsc.edu
From: Roger Jelliffe
Subject: Re: PharmPK Fatty acid pharmacokinetics
Mime-Version: 1.0
Dear Abedel-nasser:
You do not have to do the bioavailability study that way, comparing the
AUC's. You can give an intermixed regimen of IV and PO dosing, and F, the
fraction of the PO dose absorbed, is a parameter that can be obtained. This
can be done, for example, with the NPEM nonparametric population modeling
software, using linear PK models on the PC, or nonlinear PK/PD models on a
Cray T3E. The structural model will depend on how you wish to set it up.
You will parameterize the model as you see fit, including F. Then, what you
get will be not only the mean, SD, median, mode, etc. of the various
parameter values, but also the entire discrete probability density function
of the parameters, including F. It is a much easier way to do a
bioavailability study, rather that the 2 separate studies usually done to
get the 2 AUC's to compare, and there is much less chance of the parameter
values changing, as the dosage regimen can be thoroughly intermixed between
IV and PO.
Sincerely,
Roger Jelliffe
************************************************
Roger W. Jelliffe, M.D.
USC Lab of Applied Pharmacokinetics
CSC 134-B, 2250 Alcazar St, Los Angeles CA 90033
Phone (213)342-1300, Fax (213)342-1302
email=jelliffe.-at-.hsc.usc.edu
************************************************
Take a look at our Web page for announcements of
new software and upcoming workshops and events!!
It is http://www.usc.edu/hsc/lab_apk/
************************************************
---
From: "Lands, William"
To: "'PharmPK.aaa.pharm.cpb.uokhsc.edu'"
Subject: Fatty acid pharmacokinetics
Date: Thu, 15 Jan 1998 09:35:06 -0500
X-Priority: 3
The concept of either bioavailability or AUC for an endogenous fatty
acid seems strange! Is there no exogenous supply?? Even if something
were calculable for an endogenously formed material, to what purpose
would one put the resulting value?? An often overlooked problem is that
the adipose tissue reservoir of fatty acids in humans is so vast that it
may take two years to equilibrate with an exogenous acid!! Overall, the
purpose and objective of the AUC needs clarification!
_____________
Bill Lands
Voice = (301) 443-0276
FAX = (301) 594-0673
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