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The following message was posted to: PharmPK
Dear All,
We do plasma protein binding by equilibrium dialysis method using
phosphate buffer saline (pH 7.4) in one compartment and plasma in
another. The problem we are facing is the increase in plasma volume and
a decrease in buffer volume at the end of 6 hrs. This volume shift is
even upto 50%. Has anybody encountered such kind of problem and any
suggestion on how this shift can be minimized?
Thanks in advance.
Regards
Tripta Bansal
Ranbaxy Research Laboratories
India.
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Dear Dr. Bansal,
This is a well known old problem with this technique and is one of the
drawback of this method. Go through these papers to solve your problem.
1: Lapicque F, Netter P, Monot C, Bannwarth B, Maknassi MS, Royer RJ.
[Determination of protein binding of drugs using equilibrium dialysis.
Influence of volume displacement caused by osmotic pressure]
J Pharmacol. 1986 Jul-Sep;17(3):295-300. French.
2: Curry SH, Hu OY.
Evaluation of equilibrium dialysis volume shifts: a comment.
J Pharmacokinet Biopharm. 1984 Aug;12(4):463-5.
3: Tozer TN, Gambertoglio JG, Furst DE, Avery DS, Holford NH.
Volume shifts and protein binding estimates using equilibrium
dialysis:
application to prednisolone binding in humans.
J Pharm Sci. 1983 Dec;72(12):1442-6.
4: Huang JD.
Er!
rors in estimating the unbound fraction of drugs due to the volume
shift in
equilibrium dialysis.
J Pharm Sci. 1983 Nov;72(11):1368-9. No abstract available.
5: Lima JJ, MacKichan JJ, Libertin N, Sabino J.
Influence of volume shifts on drug binding during equilibrium
dialysis:
correction and attenuation.
J Pharmacokinet Biopharm. 1983 Oct;11(5):483-98.
best regards,
Jagdish Jaiswal, PhD
Drug Discovery, Torrent Research Centre
India
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The following message was posted to: PharmPK
Tripta,
You can find details here of how to correct for volume shifts:
Tozer TN, Gambertoglio JG, Holford NHG. Volume shifts and protein
binding estimates using equilibrium dialysis: Application to
prednisolone binding in humans. J.Pharm.Sci. 1983;72:1442-1446.
--
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New
Zealand
email:n.holford.-at-.auckland.ac.nz tel:+64(9)373-7599x86730 fax:373-7556
http://www.health.auckland.ac.nz/pharmacology/staff/nholford/
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Dear tripta,
You may have a look on 2 papers,
Fluid shifts and other factors affecting plasma protein binding of
prednisolone by equilibrium dialysis.
F. Douglas Boudinot and William J. Jusko. Journal of Pharmaceutical
Sciences. Vol 73, No 6, 1984, pp 774-780.
Correction for volume shift during equilibrium dialysis by measurement
of protein concentration.
K. M. Giacomini, F. M. Wong & T. N. Tozer. Pharmaceutical Research.
1984. pp 179-181.
Hope it helps
Pascal Espie
DMPK
UCB Pharma
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The following message was posted to: PharmPK
To Tripta,
yes, I have encountered a similar problem. Normally, in drug kinetics,
we
assume that the plasma volume or water space in which the drug
distributes
remains constant. But in this situation this is not the case.
The way I dealt with this was to model both the changing volume of water
(plasma volume) and the changing amount of drug in the patient. A guide
to
the change in the plasma volume over time can be obtained from the
haematocrit. The changing drug concentration is then obtained by
dividing
the estimated changing quantity of drug present in the changing
distribution
space. I am sorry if I have not described this clearly. This modeling
procedure can be accomplished reasonably easily using WinSAAM. WinSAAM
can
be downloaded for free from the following website: www.WinSAAM.com
Hope this helps.
Regards,
Peter Moate
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The following message was posted to: PharmPK
16/12/04
Dear Tripta
It is because of osmotic difference?
regards
Dr Kurani
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