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Stereoselective pharmacokinetics of tiopronin enantiomers in rats

WANG Huan,CHEN Yuan-cheng,MA Chen,ZHOU Jia,LIU Xiao-quanCenter of Drug Metabolism and Pharmacokinetics,China Pharmaceutical University,Nanjing 210009,China  
Aim:To investigate the stereoselective pharmacokinetics of tiopronin enantiomers in rats.Methods:Following iv aministration of racemic-tiopronin and tiopronin enantiomers to rats, (-)-tiopronin and (+)-tiopronin, after being extracted from rat plasma,were subjected to pre-columen chiral derivatization,and analyzed by LC-MS.Chro-matographic analysis was performed on a Shimadzu VP-ODS C18 column (150 mm×2.0 mm,5.0 μm) using a mobile phase of methanol/water (containing 0.1 mmol/L NaCl and 5.3 mmol/L formic acid) in a mode of gradient elution at a flow rate of 0.2 mL/min.LC-MS was performed in positive ion mode with selected ion monitoring (SIM).Results:The pharmacokinetic parameters of tiopronin enantiomers after the administration of racemic-tiopronin were estimated as follows:t1/ 2 (1.49±0.57 ) h and (0.58±0.24) h; AUC0-∞ (15.17±5.95) μg/mL·h and (10.52±3.72) μg/mL·h;and CL (1.31±0.70) L/h and (1.79±0.81) L/h for (-)-tiopronin and (+)-tiopronin,respectively.The pharmacokinetic parameters of (-)-tiopronin and (+)-tiopronin after dosing of tiopronin enantiomers were estimated as follows:t1/ 2 (1.52±0.28 ) h and (0.78±0.33) h;AUC0-∞ (11.93±5.02) μg/mL·h and (6.26±1.83) μg/mL·h; and CL (0.79±0.24) L/h and (2.83±0.84) L/h,respectively.Conclusion:The findings indicate differences in the pharmacokinetic parameters between (-)-tiopronin and (+)-tiopronin,and non-occurrence of the chiral inversion in rats.Moreover,there is no significant enantiomer/enantiomer interaction when tiopronin is administered in racemic form.
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