PI‐1

AIMS To compare a new column‐based method for characterization of drug‐Pgp interactions with a more conventional model, monolayers of Caco‐2 cells. METHODS A chromatographic approach was developed for the screening of compounds for their interactions with Pgp by immobilizing membranes from cells expressing and not expressing Pgp. The comparison of these columns can be used to sort compounds with/without affinity for Pgp. The change in retention time (rt) between these columns is proportional to the strength of the interaction between the compound and Pgp. These results were compared with the behavior of the same compounds in Caco‐2 monolayers, where they were sorted by calculating the coefficient of permeability in the apical‐to‐basolateral direction (Papp A‐B ) and the ratio Papp B‐A /Papp A‐B . RESULTS 14 compounds were studied using the chromatographic and Caco‐2 methods. In the parallel chromatographic screen, the value of rt varied from 0.11 min (nicardipine) to 21.53 min (domperidone). The value of Papp B‐A /Papp A‐B among the same set of compounds ranged from 1.4 to 45.0, respectively. In almost every case, when rt exceeded 0.25 min, the value of Papp B‐A /Papp A‐B was greater than 2.0, indicating a Pgp substrate. A positive correlation between the two data sets was seen (r 2 = 0.95). CONCLUSIONS The results of this study suggest that the parallel screening of new pharmaceutical compounds on Pgp (+) and Pgp (−) open tubular columns can be interchanged with the conventional and widely used Caco‐2 model. Clinical Pharmacology & Therapeutics (2005) 79 , P7–P7; doi: 10.1016/j.clpt.2005.12.022