Hexarelin · research summary

Effect of paracellular permeation enhancers on intestinal permeability of two peptide drugs, enalaprilat and hexarelin, in rats.

Acta pharmaceutica Sinica. B · 2021. 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

In vivo rat single-pass intestinal perfusion (SPIP) study investigating the effect of paracellular permeation enhancers on peptide transport.
“This was investigated using the rat single-pass intestinal perfusion model with concomitant blood sampling.”

Subjects

Male Wistar Han rats.
“In short, male Wistar Han rats (strain 273) from Charles River Co. (Germany), weight 299–395 g, were used.”

Sample size

Six rats per study group.
“The sample size in each study group was six rats, on the basis of previous perfusion studies18,29.”

Duration

135 minutes total perfusion time, consisting of a 60-minute control period and a 75-minute test period.
“In the first part, the small intestinal segment was perfused with the isotonic control buffer solution (containing both peptide drugs at the same time, enalaprilat and hexarelin) during 60 min. In the second part of the experiment, the segment was perfused during 75 min with one each of the five test solutions”

Reported findings

Luminal hypotonicity increased blood-to-lumen clearance of 51Cr-EDTA but did not affect the lumen-to-blood transport of enalaprilat and hexarelin.
“In contrast, luminal hypotonicity did not affect the lumen-to-blood transport of enalaprilat and hexarelin.”
Paracellular permeation enhancers increased the intestinal transport of hexarelin, whereas transcellular permeation enhancers did not.
“Paracellular permeation enhancers increased the intestinal transport of the peptide drug hexarelin but there was no effect of transcellular permeation enhancers.”

Limitations stated by the authors

The study was conducted in rats using a single-pass intestinal perfusion model, which may not fully replicate human physiological conditions.
“This research was focused on improving the mechanistic understanding by using a rat single-pass intestinal perfusion (SPIP) method.”

Source: PubMed 34221875 · DOI 10.1016/j.apsb.2020.12.019 · all study summaries

Duration

135 minutes total perfusion time, consisting of a 60-minute control period and a 75-minute test period.

“In the first part, the small intestinal segment was perfused with the isotonic control buffer solution (containing both peptide drugs at the same time, enalaprilat and hexarelin) during 60 min. In the second part of the experiment, the segment was perfused during 75 min with one each of the five test solutions”

Reported findings

Luminal hypotonicity increased blood-to-lumen clearance of 51Cr-EDTA but did not affect the lumen-to-blood transport of enalaprilat and hexarelin.

“In contrast, luminal hypotonicity did not affect the lumen-to-blood transport of enalaprilat and hexarelin.”

Paracellular permeation enhancers increased the intestinal transport of hexarelin, whereas transcellular permeation enhancers did not.

“Paracellular permeation enhancers increased the intestinal transport of the peptide drug hexarelin but there was no effect of transcellular permeation enhancers.”