Hexarelin · research summary

The In Vivo Effect of Transcellular Permeation Enhancers on the Intestinal Permeability of Two Peptide Drugs Enalaprilat and Hexarelin.

Pharmaceutics · 2020. Summary drawn from the study's full text. Each statement is followed by the exact sentence it comes from. This is a research summary, not medical advice.

Study type

Single-pass intestinal perfusion study in rats
“The objective of this single-pass perfusion study in rat was to investigate the effect of SDS at 5 mg/mL and of caprate administered at different luminal concentrations (5, 10, and 20 mg/mL) and pH (6.5 and 7.4).”

Subjects

Male Wistar Han rats
“In short, male Wistar Han rats (strain 273) from Charles River Co. (Cologne, Germany), weight 270–363 g, were used.”

Sample size

Five or six rats per study group
“The sample size in each study group was five or six rats on the basis of previous perfusion studies [12,13].”

Duration

135 minutes of perfusion (60 min control, 75 min test)
“In the first part, the segment was perfused with the control buffer solution (containing enalaprilat and hexarelin but no PE) for 60 min. In the second part, the segment was perfused for 75 min with one of the five test formulations (each containing enalaprilat and hexarelin, and one PE).”

Reported findings

Neither SDS nor caprate enhanced the absorption of hexarelin
“Neither SDS nor caprate at any of the investigated luminal concentrations enhanced absorption of the larger peptide hexarelin.”
Caprate requires concentrations above saturation to enhance absorption
“These results show that caprate requires doses above its saturation concentration (a reservoir suspension) to enhance absorption, most likely because dissolved caprate itself is rapidly absorbed.”

Limitations stated by the authors

The study used a rat model which may not fully represent human physiology, and the lack of effect on hexarelin suggests current permeation enhancers are insufficient for larger peptides
“The absent effect on hexarelin may partly explain why the use of permeation enhancers for enabling oral peptide delivery has largely failed to evolve from in vitro evaluations into approved oral products.”

Source: PubMed 31991924 · DOI 10.3390/pharmaceutics12020099 · all study summaries

Duration

135 minutes of perfusion (60 min control, 75 min test)

“In the first part, the segment was perfused with the control buffer solution (containing enalaprilat and hexarelin but no PE) for 60 min. In the second part, the segment was perfused for 75 min with one of the five test formulations (each containing enalaprilat and hexarelin, and one PE).”

Reported findings

Neither SDS nor caprate enhanced the absorption of hexarelin

“Neither SDS nor caprate at any of the investigated luminal concentrations enhanced absorption of the larger peptide hexarelin.”

Caprate requires concentrations above saturation to enhance absorption

“These results show that caprate requires doses above its saturation concentration (a reservoir suspension) to enhance absorption, most likely because dissolved caprate itself is rapidly absorbed.”

Limitations stated by the authors

The study used a rat model which may not fully represent human physiology, and the lack of effect on hexarelin suggests current permeation enhancers are insufficient for larger peptides

“The absent effect on hexarelin may partly explain why the use of permeation enhancers for enabling oral peptide delivery has largely failed to evolve from in vitro evaluations into approved oral products.”