title: Determination of the stereoselectivity of chiral drug transport across Caco-2 cell monolayers.
abstract: 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 micromol/l esmolol demonstrated that the two enantiomers were transported mainly by a passive, transcellular mechanism. At concentrations of 5.0-100.0 micromol/l, enantioselective permeability of esmolol was observed. In the absorptive transport, Papp 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 micromol/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.
authors.affiliation: College of Pharmaceutical Sciences, Department of Pharmaceutical Analysis and Drug Metabolism, Zhejiang University, Hangzhou, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: He
authors.forename: Su
authors.initials: S
authors.lastname: Zeng
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000493:pharmacokinetics; D001693:Biological Transport, Active; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability; D006801:Humans; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011412:Propanolamines / Q000302:isolation & purification / Q000493:pharmacokinetics; D013237:Stereoisomerism
chemical_list: D000319:Adrenergic beta-Antagonists; D004364:Pharmaceutical Preparations; D011412:Propanolamines; C036604:esmolol