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Bioavailability is one of the most important parameters to be determined for orally administored drugs. Drug absorption across intestinal membrane, which is a complex multi-pathway process, is critical in determining oral bioavailability. There are several cell-based and noncell-based in vitro assays to assess membrane peameability. Compared to noncell-based assays, cell-based assays are more labor-intensive and expensive. Therefore, cell-based assays are often performed late in the drug discovery process. Noncell-based assays, which are rapid and low-cost, are often conducted early in the drug discovery process.

Most drugs are absorbed through intestines by passive diffusion. Parallel artificial membrane permeability assay (PAMPA) represents a fast and low cost screeening tool to predict passive diffusion properties of compounds. The PAMPA artificial membrane in our assay plate has a lipid-oil-lipid tri-layer structure constructed in the pores of a porous filter. The oil layer in the middle, which maintains a robust and stable PAMPA membrane, is ultra thin to minimize compound retention and interference with the compound permeation.

After incubation, the buffer samples in donor wells and acceptor wells are analyzed by LC-MS/MS for drug concentration. The apparent permeability of a drug in cm/s is then calculated:

CD = final drug concentration in donor well (µM)
CA =final drug concentration in acceptor well (µM)
VD = volume of drug solution added into the donor well (mL)
VA = volume of buffer added into the acceptor well (mL)
Cequilibrium = ( CD * VD + CA*VA ) / ( VD + VA ) (compound concentration across donor and acceptor wells if the membrane is 100% permeable to the compound)
S = membrane area (cm2)
t = incubation time (s)

In PAMPA assay, different burffer pH values can be assessed to mimic the conditions in the gastrointestinal tract or to overcome solubility issues.

Propranolol is used as a control in our PAMPA assay.