Determination of the stereoselectivity of chiral drug transport across Caco‐2 cell monolayers

This study aimed to determine the transport characteristics of chiral drug enantiomers across Caco‐2 cell monolayers as a model of human intestinal epithelial membrane. Esmolol was chosen as a model drug, and the study focused on the transepithelial transport of esmolol enantiomers in this in vitro model system. Separation and quantitation of ( S )‐ and ( R )‐esmolol were performed by RP‐HPLC with the use of GITC as a precolumn derivatizing agent. Bidirectional transport studies of 5.0–400.0 μmol/l esmolol demonstrated that the two enantiomers were transported mainly by a passive, transcellular mechanism. At concentrations of 5.0–100.0 μmol/l, enantioselective permeability of esmolol was observed. In the absorptive transport, P app of ( S )‐esmolol was smaller than ( R )‐esmolol and vice versa for secretory transport. The enantioselectivity disappeared when the drug concentration was increased to 200.0 μmol/l. In conclusion, the transport characteristics of ( S )‐ and ( R )‐esmolol were distinctly different. An enantioselective carrier‐mediated mechanism in addition to passive diffusion was involved in the transport process of esmolol across Caco‐2 cell monolayers. © 2005 Wiley‐Liss, Inc. Chirality