Pharmacokinetics of R‐(−)ondansetron compared with that of S‐(−)ondansetron in rats using an LC–MS/MS method

Abstract

The pharmacokinetics of R-(−)ondansetron (R-ond) compared with that of S-(−) ondansetron (S-ond) was studied in rats. R-ond and S-ond were injected intravenously into rats at a dose of 2.0 mg/kg. The stability of ondansetron enantiomers in rat was 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. The enantiomer inversions between R-ond and S-ond did not occur in rat. The pharmacokinetic parameters (t 1/2 , AUC, MRT, CL) of R-ond and S-ond differed significantly. The concentration in plasma of the R/S-enantiomeric ratio reached a maximum value of 9.5 at 4.0 h post-dose.The pharmacokinetics of R-ond and S-ond are stereoselective in rat, which indicates substantial stereoselectivity in the disposition of ondansetron enantiomers in rat.R-ond has more potential than S-ond to be developed as a single enantiomer drug.

Advances and challenges in the pharmacokinetics and bioanalysis of chiral drugs

“…-S > R S > R S > R Duan et al 28 with R(+)-isomer as pharmaceutically active, is utilized to treat opiate abusers. Because of inter-individual variability in methadone enantiomer pharmacokinetics, the R/S methadone ratios in humans varied in serum and urine.…”