Noninvasive
Evaluation of Portal-Systemic Shunting
by Glyceryl Trinitrate
O.
SLANAŘ, J. AUBRECHT, F. PERLÍK1
First Medical Department, Clinical Pharmacology
Unit, General Teaching Hospital, First Faculty of
Medicine, Charles University and 1Clinical
Pharmacology Department, Institute for
Postgraduate Medical Education, Prague, Czech
Republic
Received April 15, 2001
Accepted November 22, 2001
Summary
Portal-systemic shunting is an important
circulatory abnormality in patients with liver
cirrhosis. Glyceryl trinitrate (GTN) that is
normally subject to first pass elimination, may
exhibit higher bioavailability in these patients.
This study compares the pharmacodynamic effects
of GTN after peroral and sublingual
administration for noninvasive assessment of
shunting. Six control subjects and 15 patients
with cirrhosis were studied after oral and
sublingual application of 0.5 mg of GTN. Liver
cirrhosis was complicated by portal hypertension
in 7 of the patients and 4 patients had
surgically implanted portocaval anastomosis.
Digital plethysmography, which is highly
sensitive and is essentially noninvasive in
nature, was used to assess and compare the
pharmacodynamic effects of GTN. The following
values of the ratio of areas under the
pharmacodynamic effects/time curve were obtained:
0.08±0.06 in healthy subjects, 0.52±0.21 in
patients with uncomplicated cirrhosis, 0.99±0.34
in patients with portal hypertension and 1.24±0.43
in patients with portal-systemic shunts. We
conclude that increased bioavailability of GTN
reflects portal-systemic shunting and might be
used providing that the pharmacodynamic data
reflect both pharmacokinetic variability and the
pharmacokinetic-pharmacodynamic interrelations.
Key
words
Plethysmography
· Portal-systemic shunting · Cirrhosis · Glyceryl trinitrate · Bioavailability
Reprint
requests
O. Slanař, First Medical Department, Clinical
Pharmacology Unit, U nemocnice 2, CZ-128 08
Prague 2, Czech Republic, email: oslan@lf1.cuni.cz
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