Enteral absorption of octreotide: absorption enhancement by polyoxyethylene‐24‐cholesterol ether

Drewe, Jürgen; Fricker, Gert; Vonderscher, Jacky; Beglinger, Christoph

doi:10.1111/j.1476-5381.1993.tb12799.x

Cited by 52 publications

(29 citation statements)

References 20 publications

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“…The results of a prior study suggested that the intestinal absorption of OCT may be increased and its bioavailability increased 23-fold by means of OCT microspheres with polyoxyethylene-24-cholesterol ether (9). Moreover, cationic polymer-chitosan and its derivatives, such as N-trimethyl chitosan chloride, could increase OCT bioavailability to five-fold (5) and chenodeoxycholic acid could increase it to 1.26%, with the absorption rate reaching 20.2% (26).…”

Section: Discussionmentioning

confidence: 99%

“…The administration methods and measurements for each group will be further specified when mentioned. The jejunum was selected in the present study as it is the main site of OCT absorption in the intestine (9). For the experiment of intrajejunal (i.j.)…”

Section: Methodsmentioning

confidence: 99%

“…Previous studies have attempted to improve the intestinal absorption of OCT by changing its chemical structure or adding an absorption enhancer to increase paracellular absorption, but with little effect (2,8,9). The elucidation of the factors that affect the oral absorption of OCT would facilitate the development of strategies to improve its absorption.…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of P-glycoprotein, multidrug resistance-associated protein 2 and cytochrome P450 3A4 improves the oral absorption of octreotide in rats with portal hypertension

Sun

Duan

Liu

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. The aim of the present study was to increase the intestinal transport of octreotide (OCT) by targeting the first-pass impact to identify a potential method for decreasing portal vein pressure (PVP) using oral OCT. Thus, the bioavailability of intestinally absorbed OCT was evaluated in normal rats and rats with portal hypertension (PH) that had been administered P-glycoprotein/multidrug resistance-associated protein 2/cytochrome P450 3A4 (P-gp/MRP2/CYP3A4) inhibitors. The mRNA and protein expression levels of P-gp, MRP2 and CYP3A4 were evaluated in normal and PH rats with or without OCT and the inhibitors using RT-PCR, western blot and immunohistochemical analyses. The potential effects of the inhibitor administration on PVP were also examined. The results suggest that P-gp, MRP2 and CYP3A4 play important roles in prohibiting the enteral absorption of OCT, particularly under a PH environment. Moreover, inhibitors of P-gp, MRP2 and CYP3A4 decrease the first-pass effects of OCT and effectively reduce PVP under PH conditions. Therefore, the present results suggest P-gp, MRP2 and CYP3A4 are key factors in the intestinal absorption of OCT. The inhibition of P-gp, MRP2 and CYP3A4 can markedly decrease the first-pass effects of OCT, and their use may facilitate the use of orally administered OCT.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Inhibition of P-glycoprotein, multidrug resistance-associated protein 2 and cytochrome P450 3A4 improves the oral absorption of octreotide in rats with portal hypertension

Sun

Duan

Liu

et al. 2016

Experimental and Therapeutic Medicine

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“…Though hydrogen bonding capacity is recognized to minimally affect the paracellular pathway, other factors may accompany the epithelium tight junctions to determine the transport of molecules, including the existence of conventional ion channels, their charge, permeability, size, and sensitivity to pH (Tang and Goodenough, 2003). Examples of therapeutic proteins that are known to permeate through paracellular pathways are octreotide, arginine vasopressin, and thyrotropin-releasing hormone (Lundin and Artursson, 1990;Drewe et al, 1993;Thwaites et al, 1993).…”

Section: Paracellular Transport Mechanismmentioning

confidence: 99%

Development of therapeutic proteins: advances and challenges

Akash¹,

Rehman²,

Tariq³

et al. 2015

Turk J Biol

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Therapeutic proteins have shown to be effective against a variety of diseases. Pharmaceutical companies are progressively focusing on research using proteins in search of novel effective therapeutics. The significant attention by researchers has resulted in considerable advances in the production and usage of therapeutic proteins in recent years. In the current study we focused on the understanding of therapeutic proteins and their impact on the human health care system. Advancements in the field of biotechnology have increased and facilitated the production of therapeutically significant proteins to combat various fatal diseases. Although proteinbased therapeutics have taken center stage in drug discovery and development and enhanced safety for human beings, certain challenges remain, including safety and immunogenicity issues, protein stability, and degradation issues. We made an attempt to discuss all possible factors that are linked with the basis of therapeutic proteins and possible challenges that are currently being faced by scientists during the development of these therapeutic proteins.

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“…In vitro permeation studies with Caco-2 cells Transport studies with Caco-2 cells grown on polycarbonate filters (Pore size 0.45 pm; Nucleopore, Cambridge, MA, U.S.A.) were performed as recently described (Drewe et al, 1993). Briefly, the cells were cultured for [12][13][14] C. is the concentration of the administered peptide at the apical cell monolayer side, A is the total surface area, and dQ/dt is the permeability rate (pg x h-).…”

Section: Lipid Membrane Interactionsmentioning

confidence: 99%

Permeation enhancement of octreotide by specific bile salts in rats and human subjects: in vitro, in vivo correlations

Fricker

Fahr

Beglinger

et al. 1996

British J Pharmacology

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1 The potential of bile salts to improve the enteral absorption of octreotide, an orally active somatostatin analogue, was investigated by a combination of in vitro, in situ and in vivo experiments. 2 Incorporation of octreotide into lipid monolayers (as measured by area increase of the monolayer at constant surface pressure using a Langmuir-Blodgett trough set-up) depended on the type of bile salt used for monolayer pre-treatment. Addition of 20 gM octreotide to the subphase containing 20 gM of the dihydroxylated bile salt ursodeoxycholate (UDCA) causes a 9% increase in area, whereas addition of octreotide to the subphase containing the 7a-enantiomer of UDCA, chenodeoxycholate (CDCA), resulted in an area increase of the lipid monolayer of 20%. Area increase by octreotide alone was not significantly different from the increase of octreotide and UDCA in combination. 3 CDCA and UDCA in combination with octreotide increased the permeability of liposomal membranes for rubidium ions, whereas octreotide alone did not significantly change the permeability. This indicates membrane distortion as a possible cause for the enhanced absorption of octreotide by bile salts. 4 In polarized Caco-2 cell monolayers octreotide exhibited a permeation coefficient of 0.008 + 0.004 cm h-'. Addition of 0.2-1% of UDCA to the apical incubation medium had no significant effect upon the permeation coefficient. In contrast, 0.2-1% CDCA in the incubation medium resulted in a significant increase (P<0.05) of the monolayer permeability of octreotide (0.015-0.037 cm h-').5 Octreotide was absorbed as the intact peptide from the gastrointestinal tract in rats with an absorption efficiency of 0.26%. Coadministration of bile salt resulted in a dose-dependent increase in absorption efficiency of the peptide up to 20.2%. The observed effect was more pronounced for CDCA than for UDCA. 6 The effect of CDCA and UDCA on octreotide absorption in vivo was assessed in a pharmacokinetic study with healthy volunteers. After oral administration of 4 mg octreotide in the presence of 100 mg bile salt, an average bioavailability of the peptide of 1.26% was achieved in the presence of CDCA, whereas in the presence of UDCA a bioavailability of only 0.13% was reached. This difference was statistically significant (P <0.01). 7 In conclusion, the co-administration of CDCA is able to enhance the enteral absorption of octreotide. The in vitro and in situ experiments were predictive for the observed effect in human subjects.

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Enteral absorption of octreotide: absorption enhancement by polyoxyethylene‐24‐cholesterol ether

Cited by 52 publications

References 20 publications

Inhibition of P-glycoprotein, multidrug resistance-associated protein 2 and cytochrome P450 3A4 improves the oral absorption of octreotide in rats with portal hypertension

Inhibition of P-glycoprotein, multidrug resistance-associated protein 2 and cytochrome P450 3A4 improves the oral absorption of octreotide in rats with portal hypertension

Development of therapeutic proteins: advances and challenges

Permeation enhancement of octreotide by specific bile salts in rats and human subjects: in vitro, in vivo correlations

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