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Pharmacokinetics of R-(-)ondansetron compared with that of S-(-)ondansetron in rats using a LC-MS/MS method.
Biomedical Chromatography : BMC 2018 November 9
AIM: To study pharmacokinetics of R-(-)ondansetron (R-ond) compared with that of S-(-)ondansetron (S-ond) in rats.
METHODS: After R-ond and S-ond were injected intravenously into rats at a dose of 2.0 mg/kg, respectively. Stability of ondansetron enantiomers in rat were determined by chiral HPLC, and the concentrations of R-ond and S-ond in plasma were determined by an LC/MS/MS method. The pharmacokinetic parameters were calculated and analyzed statistically using the t test.
RESULTS: The enantiomers inversions of between R-ond and S-ond didn't occurred in rat. The pharmacokinetic parameters (t1/2 , AUC, MRT, CL) of R-ond and S-ond differed significantly. The concentration in plasma of R/S-enantiomeric ratio reached a maximum value of 9.5 at 4.0 h postdose.
CONCLUSION: The pharmacokinetics of R-ond and S-ond are stereoselective in rat, which indicate substantial stereoselectivity in the disposition of ondansetron enantiomers in rat. R-ond is more potential than S-ond to be developed as a single enantiomer drug.
METHODS: After R-ond and S-ond were injected intravenously into rats at a dose of 2.0 mg/kg, respectively. Stability of ondansetron enantiomers in rat were determined by chiral HPLC, and the concentrations of R-ond and S-ond in plasma were determined by an LC/MS/MS method. The pharmacokinetic parameters were calculated and analyzed statistically using the t test.
RESULTS: The enantiomers inversions of between R-ond and S-ond didn't occurred in rat. The pharmacokinetic parameters (t1/2 , AUC, MRT, CL) of R-ond and S-ond differed significantly. The concentration in plasma of R/S-enantiomeric ratio reached a maximum value of 9.5 at 4.0 h postdose.
CONCLUSION: The pharmacokinetics of R-ond and S-ond are stereoselective in rat, which indicate substantial stereoselectivity in the disposition of ondansetron enantiomers in rat. R-ond is more potential than S-ond to be developed as a single enantiomer drug.
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