Noninvasive evaluation of portal-systemic shunting by glyceryl trinitrate.
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.
Slanar
O
O
First Medical Department, Clinical Pharmacology Unit, General Teaching Hospital, First Faculty of Medicine, Charles University, Prague, Czech Republic. oslan@lf1.cuni.cz
Aubrecht
J
J
Perlík
F
F
D000284:Administration, Oral; D000286:Administration, Sublingual; D000328:Adult; D003936:Diagnosis, Computer-Assisted; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications*; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin / Q000008:administration & dosage; D010991:Plethysmography; D011168:Portal System; D014652:Vascular Diseases / Q000175:diagnosis* / Q000209:etiology*; D014665:Vasodilator Agents / Q000008:administration & dosage
D014665:Vasodilator Agents; D005996:Nitroglycerin