Pharmacokinetic parameters determination

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Apparent Permeability Determination (Papp) – MDCKIIhMDR1 cell line
The Madin Darby Canine Kidney cell line stably transfected with the hMDR1 gene (MDCKIIhMDR1) that confers a high level of P-gp expression has been proposed as a useful in vitro model for qualitative prediction of CNS penetration of test compounds. This model is able to distinguish between compounds that pass the Blood Brain Barrier (BBB) by passive diffusion and those that are substrates for active efflux by P-gp. According to the apparent permeability (Papp) value obtained, test compounds can be classified as follows:
Papp > 150 nm/s:  high absorption
Papp 50-150 nm/s: medium absorption
Papp < 50 nm/s: low absorption
P-gp efflux can be determined by evaluation of the Papp ratio B→A/A→B, suggested values are:
B→A/A→B < 2: no/low efflux;
B→A/A→B 2-5: moderate efflux;
B→A/A→B > 5: strong efflux.