Comparison of Drug Permeabilities and BCS Classification: Three Lipid-Component PAMPA System Method versus Caco-2 Monolayers

Abstract

A three lipid-component parallel artificial membrane permeability assay (PAMPA) system was previously devised and evaluated (1). Denoted A-PAMPA for anionic-PAMPA, A-PAMPA was designed to mimic the lipid composition of the enterocyte's plasma membrane and included 1,2-dioleoyl-sn-glycero-3-[phospho-l-serine] (PS18:1) as an anionic lipid component. A-PAMPA also consists of 1,2-dioleoyl-sn-glycero-3-phosphocholine (PC18:1) and cholesterol. Metoprolol flux across A-PAMPA was measured, as well as across three other PAMPA systems (1). Results indicated that metoprolol transport across A-PAMPA was dominated by an ion-pair-mediated mechanism (i.e., metoprolol-PS18:1 complex). The objective in the present study was to compare the performance of this three lipid-component PAMPA system to Caco-2 monolayers, in terms of screening for drug permeability values. Several development laboratories employ PAMPA membranes in candidate selection, in part because of other experimental approaches, such as Caco-2 and MDCK monolayers, are more labor-intensive and expensive (2–8). However, A-PAMPA has not been previously evaluated to identify drugs that are likely to exhibit high permeability in Caco-2 BCS testing.