Parallel artificial membrane permeation

Kansy, M., Senner, F., Gubemator, K. Physicochemical high throughput screening parallel artificial membrane permeation assay in the description of passive absorption processes. /. Med. Chem. 1998, 43, 1007-1010. 

PAMPA parallel artificial membrane permeation assay... 

The evaluation of the apparent ionization constants (i) can indicate in partition experiments the extent to which a charged form of the drug partitions into the octanol or liposome bilayer domains, (ii) can indicate in solubility measurements, the presence of aggregates in saturated solutions and whether the aggregates are ionized or neutral and the extent to which salts of dmgs form, and (iii) can indicate in permeability measurements, whether the aqueous boundary layer adjacent to the membrane barrier, Umits the transport of drugs across artificial phospholipid membranes [parallel artificial membrane permeation assay (PAMPA)] or across monolayers of cultured cells [Caco-2, Madin-Darby canine kidney (MDCK), etc.]. 

There are several approaches to estimating absorption using in vitro methods, notably Caco-2 and MDCK cell-based methods or using methods that assess passive permeability, for example the parallel artificial membrane permeation assay (PAMPA) method. These are reviewed elsewhere in this book. The assays are very useful, and usually have an important role in the screening cascades for drug discovery projects. However, as discussed below, the cell-based assays are not without their drawbacks, and it is often appropriate to use ex vivo and/or in vivo absorption assays. 

The use of artificial membranes to investigate passive permeation processes has a long history, going back more than 40 years [68], The parallel artificial membrane permeation assay (PAMPA) is an application of the filter-supported lipid membrane system [149] and was first introduced by Kansy and... 

Batzl-Hartmann C, Hurst L, Maas R (2002) Method for the improvement of parallel artificial membrane permeation assay (PAMPA) by using an additional hydrophilic membrane. German Patent Application 4. 

Sugano K, Hamada H, Machida M, Ushio H (2001a) High-throughput prediction of oral drug absorption Improvement of the composition of the lipid solution used in parallel artificial membrane permeation assay. J Biomol Screen 6 189-196. 

Solubility and permeability were measured by a high throughput solubility assay and parallel artificial membrane permeation assay (PAMPA), respectively [56], The assays categorized 14 out of 18 drugs based on the BCS consistent with their known solubility and permeability characteristics [56],... 

HTS plates permit to determine drug permeability across a cell monolayer with a throughput similar to that of the parallel artificial membrane permeation assay (PAMPA), which measures rate of diffusion across a lipid layer.46 As is the case with PAMPA, the tiny surface area of the filters of the 96-well HTS presents an analytical challenge for compounds with low-to-moderate permeability. 

Artificial Membrane Methods Used to Estimate Drug Absorption 9.7.1 Parallel Artificial Membrane Permeation Assay... 

Another in vitro method for permeability screening was parallel artificial membrane permeation assay (PAMPA) initially reported by Kansy. In a PAMPA permeability screen, the Caco-2 cell mono-layer membrane is replaced by an artificially generated membrane. Versions of different artificial membranes that lack active transporter systems and pores have been developed to mimic the in vivo transcellular intestinal epithelial cell barrier. Therefore, the PAMPA screen only measures the intrinsic... 

Kong, R., Dong, D., Amstrong, T., Vallejo, M. and Wetzel, J., High Throughput Parallel Artificial Membrane Permeation Assay Using LC/MS, American Society for Mass Spectrometry 2002 Conference Abstract, Orlando, FL, USA, 2002. 

Kansy M., Sermer, F. and Gubernator, K. (1998) Physicochemical High Throughput Screening Parallel Artificial Membrane Permeation Assay in the Description of Passive Absorption Processes. Journal of Medicinal Chemistry, 41, 1007-1010. 

Parallel Artificial Membrane Permeation Assay Recent Progress... 

One decade has passed since the parallel artificial membrane permeation assay (PAM PA) was first introduced in 1998 [47]. Since then, PAM PA rapidly gained wide popularity in drug discovery [3, 48-51]. Today, PAMPA is the most widely used physicochemical membrane permeation model. The term PAMPA is nowusedas the general name for a plate-based (HTS enabled), biter-supported (filter immobilized) artificial membrane. Typically, phospholipids dissolved in an organic solvent are impregnated into the filter to construct a PAMPA membrane. 

Several in vitro assays using filter immobilized artificial membranes exist for the estimation of permeability (Parallel artificial membrane permeation assay, PAMPA). In these assays the permeation of a compound is followed directly by estimating the amount of compound on either side of the membrane barrier. The results of these experiments are expressed as permeability values rather than lipophilicity values. 

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