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Scientific article
English

HDM-PAMPA to predict gastrointestinal absorption, binding percentage, equilibrium and kinetics constants with human serum albumin and using 2 end-point measurements

Published inEuropean journal of pharmaceutical sciences, vol. 97, p. 143-150
Publication date2017
Abstract

The parallel artificial membrane permeability assay (PAMPA) is a high-throughput screening (HTS) technique developed to predict passive permeability through numerous different biological membranes, such as the gastrointestinal tract (GIT), the blood brain barrier (BBB), and the dermal layer. PAMPA is based on an artificial membrane, such as hexadecane (HDM), which separates two compartments (i.e., a donor and an acceptor compartment). In the present study, an HDM-PAMPA method was developed with human serum albumin (HSA) under iso-pH and gradient-pH conditions to predict the percentage of binding, dissociation/association constants (Kd and Ka, respectively) and dissociation/association kinetic rates (koff and kon, respectively) between a given drug and HSA. Thanks to the kinetic properties of PAMPA, a two end-point assay was implemented to obtain all three properties. The assay was used to measure basic, acidic, and amphoteric compounds. The protein was free in solution, allowing a direct comparison between this assay and equilibrium dialysis (ED). The developed PAMPA enabled screening of up to 96 compounds in a single run, generating valuable information on absorption and distribution in a high-throughput and high-repeatable manner.

Keywords
  • Passive permeability
  • PAMPA
  • Gastrointestinal tract absorption
  • Binding percentage
  • Dissociation/association constants
  • Dissociation/association microconstants
  • Human serum albumin
Citation (ISO format)
BUJARD, Alban et al. HDM-PAMPA to predict gastrointestinal absorption, binding percentage, equilibrium and kinetics constants with human serum albumin and using 2 end-point measurements. In: European journal of pharmaceutical sciences, 2017, vol. 97, p. 143–150. doi: 10.1016/j.ejps.2016.11.001
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ISSN of the journal0928-0987
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Creation03/09/2017 6:10:00 PM
First validation03/09/2017 6:10:00 PM
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