The organ extraction and splanchnic haemodynamic effects of octreotide in cirrhotic patients.
BACKGROUND
Intravenous octreotide is an established treatment of oesophageal variceal haemorrhage in the cirrhotic patient.


OBJECTIVE
To examine the organ extraction and splanchnic haemodynamic effects of octreotide in cirrhotic patients with portal hypertension.


METHODS
Thirteen patients with cirrhosis had hepatic venous catheterization performed. Hepatic venous pressure gradient (HVPG), indocyanine green (ICG) clearance and hepatic blood flow (HBF) were determined in the basal state and during 60 min of octreotide infusion by bolus injection (0.75 microg/kg) followed by continuous infusion of 0.75 microg/kg x h. Blood samples were simultaneously drawn from the femoral artery and the hepatic and renal veins.


RESULTS
The extraction fraction of octreotide in the liver was 0.05 (-0.01 - 0.14) (median (interquartile range)) and in the kidneys 0.16 (-0.06 - 0.35). The extraction fraction ratio (E(liver)/E(kidney)) was 0.69 (-0.20 - 1.06). Hepatic clearance was 47 mL/min (3-88) (n = 11). No correlations were found between liver biochemistry or galactose elimination capacity (GEC; a metabolic measure of liver function) and renal extraction fraction or liver clearance. Octreotide had no effect on HVPG or wedged hepatic venous pressure although free hepatic venous pressure increased during octreotide infusion: 6 mmHg (5-9) vs. 7 mmHg (6-10) (P = 0.02). No effect on HBF was observed while ICG clearance decreased significantly.


CONCLUSIONS
Octreotide is extracted in cirrhotic patients by both the liver and the kidney, the latter being the most important organ of elimination. Octreotide decreases liver metabolic activity determined by the ICG clearance technique, but no significant effects of octreotide on HVPG or HBF could be demonstrated.
Department of Medicine V, Aarhus University Hospital, Centre for Clinical Pharmacology at the University of Aarhus, Denmark. lo@farm.au.dk
L H
LH
Ottesen
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Flyvbjerg
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Møller
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Bendtsen
D000328:Adult; D004396:Coloring Agents / Q000493:pharmacokinetics; D005260:Female; D005765:Gastrointestinal Agents / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006975:Hypertension, Portal / Q000188:drug therapy / Q000378:metabolism; D007208:Indocyanine Green / Q000493:pharmacokinetics; D007262:Infusions, Intravenous; D008102:Liver Circulation / Q000187:drug effects*; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D008111:Liver Function Tests; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D015282:Octreotide / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D011863:Radioimmunoassay
D004396:Coloring Agents; D005765:Gastrointestinal Agents; D007208:Indocyanine Green; D015282:Octreotide