Study On Pharmacokinetic Of Zolmitriptan

PARTⅠPharmacokinetic of Zolmitriptan Tablets and effects of Compound DANSHEN Tablets,Fluvoxamine on its pharmacokinetics in rats.Object To study pharmacokinetic of Zolmitriptan tablets and effects of Compound DANSHEN Tablets,Fluvoxamine on its pharmacokinetics in rats.Methods Thirty Sprague-Dawley rats,The mean body weight was(271.38±8.62)g,The rats were were randomly assigned to 3 groups(each group was ten rats,groupⅠ:Zolmitriptan, groupⅡ:Zolmitriptan+Compound DANSHEN Tablets,groupⅢ: Zolmitriptan+ Fluvoxamine),Ten rats(groupⅠ)were administered with zolmitriptan(5.0mg.kg^-1.d^-1,ig) and the plasma concentrations of zolmitriptan in different time was determined by HPLC-MS;Ten rats (groupⅡ) were administered Compound DANSHEN Tablets(270mg^-1.kg^-1.d^-1,ig )for seven days.At the eighth day, Zolmitriptan was concurrently administered.Plasma concentrations of zolmitriptan was determined by the same methods;Ten rats(groupⅢ) were administered Fluvoxamine(10mg^-1.kg^-1d^-1,ig)for six days.At the seventh day,Zolmitriptan was concurrently administered.Plasma concentrations of zolmitriptan was determined by the same methods,The pharmacokinetic parameters were processed by 3P97 pharmacokinetics Program(Version 97,3P97).Results The plasma concentration-time curve of Zolmitriptan was fitted in well with a two-compartment open model with a lag time,After the co-administration with Compound DANSHEN Tablets,mean concentrations of Zolmitriptan in plasma were decreased throughout all sampling points.C_max,AUC_0～24,T_max,V,Cl of Zolmitriptan after single administration were significantly different from those in combination with Compound DANSHEN Tablets(p＜0.05),C_max was decreased from(550.01±15.09)ng.mL^-1 to(501.78±2.64)ng.mL^-1, AUG_0～24 was decreased from(3209.62±88.11) ng.mL^-1.h to(2793.89±41.97)ng.mL^-1.h,T_max was increased from(1.70±0.03)h to(1.85±0.11)h,V was increased from(1.46±0.16) L to(1.65±0.09) L,Cl was increased from(0.50±0.01)L.h^-1 to(0.57±0.01)L.h^-1;After the co-administration with Fluvoxamine,mean concentrations of Zolmitriptan in plasma were increased throughout all sampling points. C_max,AUG_0～24,T_1/2β,T_max,Cl of Zolmitriptan after single administration were significantly different from those in combination with Fluvoxamine (p＜0.01),C_max was increased from(550.01±15.09 )ng.mL^-1 to(620.16±16.42) ng.mL^-1,AUC_0～24 was increased from(3209.62±88.11) ng.mL^-1.h to(3641.78±305.53 )ng.mL^-1.h,T_1/2β was increased from(5.52±1.23)h to(7.63±2.38 )h,T_max was decreased from(1.70±0.03)h to(1.49± 0.12)h,Cl was decreased from(0.50±0.01)L.h^-1 to(0.42±0.01)L.h^-1.Conclusions Mean concentrations of Zolmitriptan in plasma were decreased throughout all sampling points After the co-administration with Compound DANSHEN Tablets,Compound DANSHEN Tablets may be induce the metabolism of Zolmitriptan in vivo;Fluvoxamine markedly inhibits the metabolism of Zolmitriptan in vivo,CYP1A2 may be one of the major oxidative enzymes for the disposition of Zolmitriptan in vivo. It is recommend that the Close observation and the benefit-risk evaluation should be paid when the CYP1A2-involved drug is combined with Zolmitriptan therapy.PARTⅡPharmacokinetic and Relative Bioavailability of Zolmitriptan Tablets in healthy Chinese volunteersObject To determine zolmitriptan in human plasma by HPLC-MS method and study its pharmacokinetics and Relative Bioavailability.Methods Twenty healthy adult male volunteers participated in this 2 periods,2 sequences crossover study.The volunteers were randomLy assigned to 2 groups and were administered with a single oral dose of 5 mg zolmitriptan tablet(test or reference drug) in each stage, serial blood samples were collected for a period of 24 h,Plasma was separated and the concentration of zolmitriptan in human plasma was determined by HPLC-MS,The pharmacokinetic parameters were processed by 3P97 pharmacokinetics Program(Version 97,3P97),The bioequivalence of the two formulations were compared by two one-side t-test.Results The plasma concentration-time curves of the test and reference drug were fitted in well with a two-compartment open model with a lag time,The C_max,T_max,AUC_0～24,T_1/2β,V,Cl of the test and reference drug were(11.38±3.06)ng.mL^-1 and(11.33±3.16 )ng.mL^-1,(2.0±0.49)h and(1.98±0.50)h,(57.35±12.38 )ng.mL^-1.h and(56.27±11.55) ng.mL^-1.h,(3.51±0.97)h and(3.36±0.89)h,(283.00±85.38)L and(305.7±90.79)L,(84.34±19.82) L.h^-1 and(89.79±18.93 )L.h^-1,The relative bioavailability was(102.7±15.4)%.Conclusions The analytical method for zolmitriptan was found to be rapid,sensitive and suitable for application in pharmacokinetic studies and routine determination of numerous samples,No significant difference exists among the main pharmacokinetic parameters for the test and reference drug.The two formulations were bioequivalent.