PAMPA polycarbonate filters

Faller and Wohnsland [509,554] developed the PAMPA assay using phospholipid-free hexadecane, supported on 10-pm thick polycarbonate filters(20% porosity,... 

Faller and Wohnsland [18, 19] developed the PAMPA assay using phospholipid-free hexadecane, supported on 10 pm-thick polycarbonate filters, and were able to demonstrate interesting predictions. Their PAMPA method appeared to be a satisfactory substitute for obtaining alkane/water partition coefficients, which are usually very difficult to measure directly, due to the poor solubility of drug molecules in alkanes. Apparently, membrane retention was not measured. 

On the other hand, PAMPA is a purely artificial method and PAMPA membranes do not reassemble real lipid bilayer structures as barriers for permeation but much thicker barriers. The thickness and material of the supporting PVDF filters also influences artificially the permeation of compounds depending on the lipophilicity of the compounds more than the thin polycarbonate filter does in CACo2 experiments. Also the best choice of membrane constituents for PAMPA experiments is still under investigation and it seems that it will depend a lot on the goal of the PAMPA experiment which membrane is used (e.g. blood brain barrier permeation or intestinal absorption). One has to take into account that PAMPA today is a summary term on a lot of different methods applied in different laboratories using different membrane constituents, sink conditions, permeation times etc., which makes inter laboratory comparison difficult. 

In the same way, o-nitrophenyl octyl ether (o-NPOE) was immobilized on polycarbonate (PC) filters and the apparent permeability measured after 5 h incubation time was correlated to log Pnpoe for a series of reference compounds (log Pnpoe ranging from —1 to 3.6) [90]. Lipophilicity values in the alkane/water system were also determined using PAMPA with hexadecane-PC coated filters [89]. In this case, a correlation was found between intrinsic permeability (log Pq, permeability corrected for ionization and for unstirred water layer contribution, which particularly affects permeability of lipophilic compounds) and log P ik. However, log Pq is obtained from the knowledge of the pJC, value(s) and the permeability pH profile and therefore requires the full permeability pH profile to be measured for each compound, which negatively impacts the assay throughput. 

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