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Dear All
I am in the process of writing a protocol for a conventional PK study
in diabetic patients. As you may know diabetes may influence drug
absorption due to changes in the gastric emptying time which is
secondary to diabetic neuropathy (gastric paresis). I was wondering if
there is any minimally invasive method to evaluate gastric emptying
time and/or any grading system for gastric paresis?
Many thanks in advance.
Fatemeh Akhlaghi, PharmD, PhD
Assistant Professor
Applied Pharmaceutical Sciences
University of Rhode Island
125 Fogarty Hall, 41 Lower College Road
Kingston, RI 02881
USA
Email: fatemeh.aaa.uri.edu
Laboratory Website:
http://www.uri.edu/pharmacy/faculty/aps/akhlaghi/index
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Gastric emptying can often be measured by given a single dose
acetaminophen to measure the peak time (see couple articles beblow).
1: Kamiya T, Kobayashi Y, Hirako M, Misu N, Nagao T, Hara M, Matsuhisa
E, Ando T, Adachi H, Sakuma N, Kimura G. Related Articles, Links
Gastric motility in patients with recurrent gastric ulcers.
J Smooth Muscle Res. 2002 Apr;38(1-2):1-9.
PMID: 12199528 [PubMed - in process]
2: Wong CA, Loffredi M, Ganchiff JN, Zhao J, Wang Z, Avram MJ. Related
Articles, Links
Gastric emptying of water in term pregnancy.
Anesthesiology. 2002 Jun;96(6):1395-400.
PMID: 12170052 [PubMed - indexed for MEDLINE]
Sam Liao, Ph.D.
PharMax Research
270 Kerry Lane,
Blue Bell, PA 19422
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Dear Fatemeh Akhlaghi,
you can prove the Acetaminophen or Paracetamol Absorbtion Test.
The problem of this test is that does not exit a well-defined protocol
and
target, as you can easily read in several publications.
But from a pharmacokinetic point of view it is correct.
Best regards,
Prof. Massimo Baraldo
Massimo Baraldo, MD
Associate Professor of Pharmacology
Clinical Pharmacologist
Institute of Clinical Pharmacology and Toxicology
Medical School
University of Udine
P.le SM Misericordia, 3
33100 Udine
Italy
email: massimo.baraldo.-at-.dpmsc.uniud.it
URL:http://www.uniud.it/ifct/welcome.html
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Dear Fatemeh
There is indeed a minimally invasive method of measuring gastric
emptying
called epigastric impedance. It passes a very small alternating
electric
current through the gastric zone and only requires 3 electrodes stuck
onto
the anterior and posterior abdominal skin. A prototype was used in
diabetics
with gastroparesis several years ago (see Gilbey SG & Watkins PJ 1987
Diabetic Medicine 4, 122-126) and detected a significantly slower rate
of
emptying in diabetics (p< 0.01) However, actual delayed gastric empting
was
not uniform in those who had symptoms of gastroparesis though some had a
very delayed t50% for water longer than 30 minutes.
The technique has also been used during migraine attacks and in
neonates, a
testimony to its non-invasiveness. It is restricted to liquids that are
either very unconductive (eg: water or glucose solutions) or very
conductive
(eg: salty tomato juice) because isoconductive liquids or solid foods
do not
show up when the stomach fills. Also complex meals provoke gastric
secretions which produce a variable artefact.
Water test "meals" do make a useful "probe" as they detect changes in
gastric emptying when you would expect them, ie: faster emptying on
upright
or lying on right side postures vs supine or on left side postures,
after
prokinetics or gastric delayers like morphine. In fact when Murphy et al
(Anesthesiology 1997, 87: 765-770) gave morphine to volunteers emptying
slowed down almost four fold and it was verified by simultaneous
paracetamol
(acetaminophen) absorption. We have also found that epigastric
impedance
detects gastric contractions and by using a technique to analyse the
signal
which is similar to EEGs, we find we can quantify the response to a test
meal. The response has been shown to increase when a prokinetic like
metoclopramide is given.
The problem with other non-invasive techniques like paracetamol
absorption
or C13 octanol is that they do not actually measure gastric emptying.
They
only tell you if one occasion was faster or slower than another or
possibly
a population average. Scintigraphy is the only really established direct
method. With modern techniques using Technetium 99 the radiation
exposure is
about the same as a flight from London to Cape Town so it is very
small, so
you can repeat it to monitor progress. The main problems with it is the
sheer expense and the time taken of highly skilled operators.
Having tried to organise further trials I found that diabetics with
gastroparesis due to neuropathy are rare (which I'm actually glad about
because it is s very distressing condition). I suggest that your best
recourse is to just do the study in your population and actually measure
your pk parameters and compare them with normal volunteers.
Hope this helps
Andrew Sutton.
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)