The pharmacokinetics of oxiracetam and its degraded substance(4-hydroxy-2-oxo-1-pyrrolidine acetic acid,HOPAA)after oral and intravenous administration in rats were studied using an established UPLC-MS/MS method.Three...The pharmacokinetics of oxiracetam and its degraded substance(4-hydroxy-2-oxo-1-pyrrolidine acetic acid,HOPAA)after oral and intravenous administration in rats were studied using an established UPLC-MS/MS method.Three groups of rats after an overnight fasted received 10 g/kg(n=6)oxiracetam suspensions orally,and 2 g/kg(n=6)normal or degraded oxiracetam injections intravenously via a caudal tail vein,respectively.Before the pharmacokinetic experiment,a simple safety evaluation testwas conducted on the degraded oxiracetam injections containing 16.16% HOPAA in mice.There was no mortality by a single intravenous dose of 2 g/kg of degraded oxiracetam injections within twoweeks,demonstrating that HOPAA was non-toxic in mice.Following intravenous administration of the normal injections,the plasma concentration-time curves of oxiracetam and HOPAA both showed a rapid elimination phase.The values of t_(1/2)were 3.1±1.5 h for oxiracetamand 0.8±0.2 h for HOPAA,andthemean residencetimes(MRT)were 1.2±0.1h and 0.8±0.1h,respectively.Oxiracetam and HOPAA after intravenous administration of the degraded oxiracetam injections presented elimination patterns similar to those observed in the normal injections.Oral pharmacokinetic results showed that the Tmax was less than 1.5 h for the two analytes,and both had a longer t_(1/2) and MRT than those of intravenous administration.Contents of HOPAA in three groupswere calculated based on AUC_(0-t) values of the two analytes.The quantitative change of HOPAA in vivo was also evaluated by comparing the plasma concentrations of HOPAA and oxiracetamat the same time for every group.Additionally,the values of absolute bioavailability of oxiracetam were about 8.0%and 7.4%calculated by the normal or degraded oxiracetam injections,whichwere far less than the value of 75%reported in literature,indicating the necessity of further study.展开更多
基金This work was financially supported from the National Nature Science Foundation of China(No.81173009).
文摘The pharmacokinetics of oxiracetam and its degraded substance(4-hydroxy-2-oxo-1-pyrrolidine acetic acid,HOPAA)after oral and intravenous administration in rats were studied using an established UPLC-MS/MS method.Three groups of rats after an overnight fasted received 10 g/kg(n=6)oxiracetam suspensions orally,and 2 g/kg(n=6)normal or degraded oxiracetam injections intravenously via a caudal tail vein,respectively.Before the pharmacokinetic experiment,a simple safety evaluation testwas conducted on the degraded oxiracetam injections containing 16.16% HOPAA in mice.There was no mortality by a single intravenous dose of 2 g/kg of degraded oxiracetam injections within twoweeks,demonstrating that HOPAA was non-toxic in mice.Following intravenous administration of the normal injections,the plasma concentration-time curves of oxiracetam and HOPAA both showed a rapid elimination phase.The values of t_(1/2)were 3.1±1.5 h for oxiracetamand 0.8±0.2 h for HOPAA,andthemean residencetimes(MRT)were 1.2±0.1h and 0.8±0.1h,respectively.Oxiracetam and HOPAA after intravenous administration of the degraded oxiracetam injections presented elimination patterns similar to those observed in the normal injections.Oral pharmacokinetic results showed that the Tmax was less than 1.5 h for the two analytes,and both had a longer t_(1/2) and MRT than those of intravenous administration.Contents of HOPAA in three groupswere calculated based on AUC_(0-t) values of the two analytes.The quantitative change of HOPAA in vivo was also evaluated by comparing the plasma concentrations of HOPAA and oxiracetamat the same time for every group.Additionally,the values of absolute bioavailability of oxiracetam were about 8.0%and 7.4%calculated by the normal or degraded oxiracetam injections,whichwere far less than the value of 75%reported in literature,indicating the necessity of further study.
