Stereoselective transport and uptake of propranolol across human intestinal Caco‐2 cell monolayers

The transport and uptake of individual propranolol (PPL) enantiomers were studied in human intestinal Caco‐2 cell monolayers, and a reversed‐phase HPLC‐UV assay was used for quantitative analysis. S‐PPL and R‐PPL across Caco‐2 cell monolayers was determined in the concentrations range of 10–500 μM in both apical (AP) to basolateral (BL) and BL to AP directions. S‐PPL exhibited greater permeability than R‐PPL in the AP to BL direction, whereas in the BL to AP direction S‐enantiomer transported less than R‐enantiomer. Uptake of R‐PPL was significantly higher than that of S‐PPL either from AP side or from BL side. The statistically significant differences in uptake were observed at the concentrations range from 10 to 50 μM. Furthermore, the apparent Michaelis constant (K_m) and maximal velocity (V_max) also showed significant difference between the two enantiomers. Moreover, the AP to BL transport of PPL enantiomer was markedly decreased by lowering the pH of the apical side but it did not affect the stereoselectivity of PPL across Caco‐2 cell monolayers. The transport and uptake of PPL in the BL to AP direction was not influenced by several protein inhibitors. The results suggest that PPL enantiomers showed stereoselective transport and uptake across the Caco‐2 cell monolayers. A special transport mechanism capable of directing the PPL enantiomers might be present in the Caco‐2 monolayers. Chirality 2010. © 2009 Wiley‐Liss, Inc.