• Home
  1. Home
  2. Modification of a PAMPA model to predict passive gastrointestinal absorption and plasma protein binding
Scientific article
English

Modification of a PAMPA model to predict passive gastrointestinal absorption and plasma protein binding

Contributors

Bujard, Alban; Voirol, Hervé; Carrupt, Pierre-Alain; Schappler, Julie

Published in

European journal of pharmaceutical sciences, vol. 77, p. 273-278

Publication date

2015

Abstract

The Parallel Artificial Membrane Permeability Assay (PAMPA) is a well-known high throughput screening (HTS) technique for predicting in vivo passive absorption. In this technique, two compartments are separated by an artificial membrane that mimics passive permeability through biological membranes such as the dermal layer, the gastrointestinal tract (GIT), and the blood brain barrier (BBB). In the present study, a hexadecane artificial membrane (HDM)-PAMPA was used to predict the binding of compounds towards the human plasma using a mixture of human serum albumin (HSA) and alpha-1 acid glycoprotein (AGP). The ratio of HSA and AGP was equivalent to that found in the human plasma for both proteins (20:1). A pH gradient (5.0–7.4) was performed to increase the screening capacity and overcome the issue of passive permeability for acidic and amphoteric compounds. With this assay, the prediction of passive GIT absorption was maintained and the compounds were discriminated according to their permeability (on a no-to-high scale). The plasma protein binding (PPB) was estimated via the correlation of the differences between the amount of compound crossing the artificial membrane in assays conducted with and without protein using only a two end-point measurement. The use of a mixture of HSA and AGP to modulate drug permeation was compared to the use of the same concentrations of HSA and AGP used separately. The addition of HSA alone in the acceptor compartment was sufficient for estimating PPB, while it was demonstrated that AGP alone could enable the estimation of AGP binding.

Keywords

  • Alpha-1-acid glycoprotein
  • Human serum albumin
  • PAMPA
  • Passive permeability

UNIGE affiliation entities

UNIGE research groups

Citation (ISO format)

BUJARD, Alban et al. Modification of a PAMPA model to predict passive gastrointestinal absorption and plasma protein binding. In: European journal of pharmaceutical sciences, 2015, vol. 77, p. 273–278. doi: 10.1016/j.ejps.2015.06.023

Main files (1)

Article (Published version)

Identifiers

Additional URL for this publication

http://linkinghub.elsevier.com/retrieve/pii/S0928098715003188

Journal ISSN

0928-0987
659views
0downloads

Technical informations

Creation

03/12/2015 10:13:00

First validation

03/12/2015 10:13:00

Update

14/03/2023 23:56:24

Status update

14/03/2023 23:56:24

Last indexation

31/10/2024 02:12:15
All rights reserved by Archive ouverte UNIGE and the University of Geneva
OpenAIRE Indexed & Validated