Frog intestinal perfusion to evaluate drug permeability: application to p-gp and XXXX substrates.

@entity1 @entity5322 @entity9886 @entity36804 @entity35 @entity1363
To evaluate the reliability of using in situ frog intestinal perfusion technique for permeability assessment of carrier transported drugs which are also substrates for CYP enzymes. Single Pass Intestinal Perfusion (SPIP) studies were performed in frogs of the species @entity36804 using established method for @entity35 with some modifications after inducing anesthesia. Effective permeability coefficient (P eff) of @entity9886 and @entity1363 was calculated in the presence and absence of inhibitors using the parallel-tube model. Peff of @entity9886 when perfused alone was found to be 0.427    0.27 * 10(-4)cm/s and when it was co-perfused with inhibitors, significant change in P eff was observed. Peff of @entity1363 when perfused alone was found to be 2.03    0.07 * 10(-4)cm/s and when it was co-perfused with inhibitors, no significant change in P eff was observed. Comparison of P eff calculated in frog with that of other available models and also @entity1 suggested that the P eff-values are comparable and reflected well with @entity1 intestinal permeability. It is possible to determine the P eff-value for compounds which are dual substrates of P-glycoprotein and @entity5322 using in situ frog intestinal perfusion technique. The calculated P eff-values correlated well with reported P eff-values of probe drugs. comparison of the P eff-value of @entity9886 obtained with that of reported @entity1 's P eff and Caco 2 cell data, and comparison of the P eff-value of @entity1363 with that of reported @entity35 's P eff, we could conclude that SPIP from model can be reliably used in preclinical studies for permeability estimation. This model may represent a valuable alternative to the low speed and high cost of conventional animal models (typically rodents) for the assessment of intestinal permeability.
