Acute effects of propylthiouracil on hemodynamics and oxygen content in patients with alcoholic cirrhosis.
OBJECTIVE
The antithyroid drug propylthiouracil has been suggested for the treatment of alcoholic liver disease. Its beneficial effects could be due to either a decrease in hepatic oxygen consumption or an increase in hepatic blood flow. The aim of this study was to test these two hypotheses in patients with proven alcoholic cirrhosis.


METHODS
The pharmacokinetic parameters after intravenous administration of 300 mg of propylthiouracyl were first determined in four patients. Then, the effects on systemic and splanchnic hemodynamics, and oxygen content were measured 45 and 90 min after the intravenous administration of 300 mg (n=6) or 600 mg (n=6) of propylthiouracil.


RESULTS
Systemic hemodynamics (heart rate, arterial pressure, cardiac output and systemic vascular resistance) and splanchnic hemodynamics (hepatic venous pressure gradient, hepatic and azygos blood flows) were not modified 45 and 90 min after the administration of 300 mg or 600 mg of propylthiouracil. Moreover, neither oxygen content in the radial artery, pulmonary artery or hepatic vein, nor systemic oxygen uptake was modified after propylthiouracyl administration. The absence of effect of propylthiouracyl administration was also confirmed in patients with cirrhosis with proven acute alcoholic hepatitis (n=7).


CONCLUSIONS
In patients with alcoholic cirrhosis, acute administration of propylthiouracyl has no effect on systemic and splanchnic hemodynamics or on oxygen contents. The presence of acute alcoholic hepatitis does not modify these results.
Sogni
P
P
Unité de Recherches de Physiopathologie Hépatique (INSERM U-24), Hôpital Beaujon, Clichy, France.
Hadengue
A
A
Moreau
R
R
Le Moine
O
O
Soupison
T
T
Oberti
F
F
Farinotti
R
R
Lebrec
D
D
D000328:Adult; D000963:Antimetabolites / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007262:Infusions, Intravenous; D008099:Liver / Q000098:blood supply; D008104:Liver Cirrhosis, Alcoholic / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010101:Oxygen Consumption / Q000187:drug effects*; D011441:Propylthiouracil / Q000008:administration & dosage* / Q000493:pharmacokinetics; D013053:Spectrophotometry; D013152:Splanchnic Circulation / Q000187:drug effects; D016896:Treatment Outcome
D000963:Antimetabolites; D011441:Propylthiouracil