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 microl) 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-infinity) and C(max) values of (+)-tenatoprazole were significantly greater than those of (-)-tenatoprazole (P < 0.001). The mean AUC(0-infinity) 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 < 0.01 and P < 0.001, respectively) values between enantiomers. This study suggests that the pharmacokinetics of tenatoprazole are enantioselective in rats.
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