Determination of tenatoprazole enantiomers and their enantioselective pharmacokinetics in rats

The enantioselective pharmacokinetics of tenatoprazole were studied in Wistar rats after the administration of a single oral dose of rac ‐tenatoprazole. Serial plasma samples were collected; and the pharmacokinetic behavior of each enantiomer was characterized using a sequential achiral and chiral liquid chromatographic method. Tenatoprazole was extracted from a small aliquot of plasma (100 μl) by one‐step extraction using hexane‐dichloromethane‐isopropanol (20:10:1, v/v/v) as extract solvent. Plasma drug concentration–time data were analyzed for each enantiomer by using a noncompartmental method. The AUC 0−∞ and C max values of (+)‐tenatoprazole were significantly greater than those of (−)‐tenatoprazole ( P < 0.001). The mean AUC 0−∞ value of (+)‐tenatoprazole was 7.5 times greater than that of (−)‐tenatoprazole after oral administration of rac ‐tenatoprazole to rats at a dose of 5 mg/kg. There are also significant differences in t 1/2 and CL/F ( P < 0.01and P < 0.001, respectively) values between enantiomers. This study suggests that the pharmacokinetics of tenatoprazole are enantioselective in rats. Chirality, 2008. © 2009 Wiley‐Liss, Inc.