Larazotide acetate — pharmacology
Molecular targets, mechanism of action, pharmacokinetics and interactions as characterised in humans.
§2Pharmacology
§2.1Molecular targets
Table 2. Molecular targets recorded for Larazotide acetate, with the character of the interaction and the potency where the Institute holds it.
| Target | Interaction | Note |
|---|---|---|
| Zonulin pathway / tight-junction assembly | Antagonist | Acts locally at the intestinal epithelial tight junction; no systemic receptor target |
§2.2Mechanism of action
Larazotide antagonises zonulin-mediated tight-junction disassembly, reducing paracellular permeability in intestinal epithelium. The therapeutic hypothesis in coeliac disease was that limiting gluten-peptide translocation across a compromised barrier would reduce symptoms in patients on a gluten-free diet with persistent symptoms.[1,2]
§2.3Pharmacokinetics
- Terminal half-life
- not applicable — negligible systemic absorption is a design objective
- Time to maximum concentration
- not applicable
- Volume of distribution
- not applicable
- Plasma protein binding
- not applicable
- Clearance
- not applicable
- Bioavailability
- minimal by design; systemic exposure is below quantifiable limits at therapeutic doses
Luminal proteolysis and faecal elimination. The Institute notes that a locally acting, non-absorbed peptide has a fundamentally different benefit–risk architecture from every other compound in this series.
§2.4Interactions
- None expected given negligible absorption
References cited on this page
References are numbered in order of first citation in this document. Each superscript in the text links to its entry below.
- D’Hondt M, Bracke N, Taevernier L, Gevaert B, Verbeke F, Wynendaele E, De Spiegeleer B. Related impurities in peptide medicines. Journal of Pharmaceutical and Biomedical Analysis 2014;101:2–30. doi:10.1016/j.jpba.2014.06.012 · PMID 25044089
- Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, Cates CJ, Cheng HY, Corbett MS, Eldridge SM, Emberson JR, Hernán MA, Hopewell S, Hróbjartsson A, Junqueira DR, Jüni P, Kirkham JJ, Lasserson T, Li T, McAleenan A. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ 2019;366:l4898. doi:10.1136/bmj.l4898 · PMID 31462531
Identifiers are reproduced only where the Institute holds them. Where a digital object identifier or PubMed identifier is not shown, the Institute has recorded the journal and year and has not constructed an identifier.