Sustained reduction of portal pressure by administration of octreotide — LAR in portal hypertensive rats

Abstract

Objective: Recent studies have demonstrated octreotide as being potentially beneficial for the long-term management of cirrhotic portal hypertension. However, its short-term effects, requiring subcutaneous administration at least twice daily, make it inconvenient, practically, for long-term therapy. Hence, the current study was undertaken to evaluate the effects of the new long-acting-release octreotide formulation (octreotide-LAR) on portal pressure in a prehepatic portal hypertensive rat model. Methods: 14 days after portal vein stenosis or sham operation, rats were treated with either octreotide-LAR (0.25 mg/kg body weight, subcutaneously) or vehicle, after the baseline portal pressure measurements were obtained in each group. On days 10, 15, 18, 21, 24, 27 and 30 post-treatment, eight rats from each sub-group (portal vein stenosis plus octreotide-LAR, or vehicle, sham-operated plus octreotide-LAR or vehicle) were subjected to portal vein pressure measurement. Results: portal vein-stenosed rats exhibited a significantly higher portal vein pressure than sham-operated rats (13.82+/-2.18 vs. 5.82+/-1.08 mmHg, P=0.0001). Octreotide-LAR treatment was found to significantly (P=0.001) reduce portal pressure in portal vein stenosed rats from the tenth post-injection day and thereafter to sustain reduction. Conclusion: the long-acting-release octreotide given in a single dose in a prehepatic portal hypertensive rat model diminishes and sustains diminished portal pressure for 20 days after the tenth post-injection day. These findings seem promising for the portal hypertensive patient and further clinical studies are necessary.