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For the determination of the bioavailablity of a nasal drug delivery
form for APOMORPHINE, comparison was made with a subcutaneous and IV
injection.
After administration of EQUAL doses , consistently a lower value for
AUC was obtained for the IV injection compared to the two other ones.
Does anyone have an explanation for this phenomenon ? The tests were
done on rabbits and sixtheen times this result was obtained.
RENAAT KINGET
PHARMACOTECHNOLOGY & BIOPHARMACEUTICS
K.U. LEUVEN
O&N , CAMPUS GASTHUISBERG
B-3000 LEUVEN
BELGIUM
TEL. 32 (0)16 345820 FAX. 32 (0)16 345996
e-mail renaat.kinget.-a-.med.kuleuven.ac.be
url:http://www.farm.kuleuven.ac.be/farm/pharbio/index.htm
------------
Prof. R. KINGET
PHARMACOTECHNOLOGY & BIOPHARMACEUTICS
K. U. Leuven, Gasthuisberg, B-3000 LEUVEN, Belgium
TEL 32(0)16 345820 FAX 32(0)16 345996
e-mail renaat.kinget.aaa.farm.kuleuven.ac.be
http://www.farm.kuleuven.ac.be/farm/pharbio/index.htm
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More information would help: From the plasma profiles, are they and
their terminal portions of (plasma vs time) the same compared to IV?
I do not know much about this drug and its metabolism and solubility,
is it highly cleared by the liver, is it very much soluble in the
blood pH?
Regards
Nabil
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[Two replies - db]
From: "Ronald A. Herman"
To:
Subject: RE: PharmPK AUC low after IV Administration
Date: Fri, 3 Sep 1999 08:53:41 -0500
X-Priority: 3 (Normal)
Importance: Normal
Renaat,
I don't know if the same applies to Apomorphine, but I know with morphine if
our first blood sample following IV administration is not within 2 minutes
of administration of the IV bolus then we miss a significant portion of our
area under the curve. What is your sampling schedule? With the SQ and
intra-nasal delivery, the absorption delays the appearance of the
apomorphine so that your sampling scheme may allow you to better detect the
concentration in that early phase, and as a result obtain a larger AUC.
Ron Herman
********************
Ronald A. Herman, Ph.D.
E-mail: Ronald-A-Herman.-at-.uiowa.edu
University of Iowa
http://r=
herman.pharmacy.uiowa.edu
S525 College of Pharmacy
Phone: 319-335-8765
Iowa City, IA 52242
Pager:=
319-356-7000 #5085
********************
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X-Sender: st005899.-at-.brandywine.otago.ac.nz
Date: Fri, 3 Sep 1999 17:49:03 +1200
To: PharmPK.-a-.boomer.org
From: Robert Purves
Subject: AUC low after IV Administration
An obvious possibility: you may have too few samples during an initial high
peak after IV, so that your area-estimation method misses out a substantial
fraction of the area at early times. Perhaps you should consider
extrapolating back to zero time from the first few measured points, in a
similar fashion to the commonly-performed extrapolation to infinity for
estimating the AUC tail area.
Robert Purves
Department of Pharmacology
School of Medical Sciences
University of Otago
P.O Box 913
Dunedin
New Zealand
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