Octreotide decreases portal pressure: Hepatic stellate cells may play a pivotal role

Background Portal hypertension (PH) is the main cause of complications and death in liver cirrhosis. The effect of oral administration of octreotide (OCT), a drug that reduces PH by the constriction of mesenteric arteries, is limited by a remarkable intestinal first-pass elimination. Methods The bile duct ligation (BDL) was used in rats to induce liver cirrhosis with PH to examine the kinetics and molecular factors such as P-glycoprotein (P-gp), multidrug resistance-associated protein 2 (MRP2) and cytochrome P450 3A4 (CYP3A4) influencing the intestinal OCT absorption via in situ and in vitro experiments on jejunal segments, transportation experiments on Caco-2 cells and experiments using intestinal microsomes and recombinant human CYP3A4. Moreover, RT-PCR, western blot, and immunohistochemistry were performed. Results Both in situ and in vitro experiments in jejunal segments showed that intestinal OCT absorption in both control and PH rats was largely controlled by P-gp and, to a lesser extent, by MRP2. OCT transport mediated by P-gp and MRP2 was demonstrated on Caco-2 cells. The results of RT-PCR, western blot, and immunohistochemistry suggested that impaired OCT absorption in PH was in part due to the jejunal upregulation of these two transporters. The use of intestinal microsomes and recombinant human CYP3A4 revealed that CYP3A4 metabolized OCT, and its upregulation in PH likely contributed to impaired drug absorption. Conclusions Inhibition of P-gp, MRP2, and CYP3A4 might represent a valid option for decreasing intestinal first-pass effects on orally administered OCT, thereby increasing its bioavailability to alleviate PH in patients with cirrhosis.

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Impact of Octreotide on Early Complications After Liver Transplant: A Randomized, Double-Blind Placebo-Controlled Trial

Lankarani¹,

Safa²,

Ghahramani³

et al. 2022

Exp Clin Transplant

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Octreotide decreases portal pressure: Hepatic stellate cells may play a pivotal role

Abstract: The aim of this study is to elucidate the effects of different dosages of octreotide on portal pressure in cirrhotic patients and to investigate the mechanism of activated human hepatic stellate cells (

Cited by 3 publications

References 16 publications

Ultrasonic diagnosis and vasoactive substances examination in patients with cirrhosis

Ultrasonic diagnosis and vasoactive substances examination in patients with cirrhosis

Overexpression of P-glycoprotein, MRP2, and CYP3A4 impairs intestinal absorption of octreotide in rats with portal hypertension

Impact of Octreotide on Early Complications After Liver Transplant: A Randomized, Double-Blind Placebo-Controlled Trial

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