Pharmacokinetics of 2,3-indolinedione in rats

Objective To study the pharmacokinetics of 2,3-indolinedione in rats after single administration of the drug orally or intravenously and to provide some information for the development of the new drug. Methods 0.25 ml blood were sampled from rats before and 5,15,30 min,1,2,4,6,8, 24 h after drug administration.The blood samples were pretreated by protein precipitation method using methanol. Quetiapine was used as internal standard. After pretreatment, the samples were assayed by LC/MS/MS mothod and the pharmacokinetic parameters were calculated by WinNonlin 5.2 using non-compartment model. Results The pharmaceutical parameters in rats after single administration of the drug orally or intravenously(average±SD)were as follow. Iv:TmaxCmaxt1/2 AUC0-t AUC0-∞Vz and CLz were (0.83±0.29)hr,(141.53±10.99)μg/L, (1.68±0.84)hr,(1068.15±389.06)μg/hr/L, (1211.19±469.18)μg/hr/L,(4.13±1.41)L/kg,(1.89±0.94)L/hr/kg;oral:TmaxCmaxt1/2 AUC0-t AUC0-∞Vz and cLz were (0.05±0.00)hr,(1725.53±469.70)ng/ml,(4.21±2.78)hr,(7711.21±2533.12)μg/hr/L,(7986.07±2623.38)μg/hr/L, the bioavailability(AUC0-t)was (57.75±18.97)%.Conclusion 2,3-indolinedione in rats after single administration of the drug orally has rapid elimination and good absorption.