国产米索前列醇不同给药途径的血药浓度变化研究

目的:比较不同给药途径国产米索前列醇在妊娠妇女体内的血药浓度变化。方法:将早期妊娠行人工流产妇女26例分为3组,术前分别采用口服(口服组)、舌下含服(舌下组)和阴道放置(阴道组)3种途径给予米索前列醇600μg。给药前及给药后15min、30min、60min、2h、12h(口服组末次取血时间为给药后3h)采集血液样本,用液相色谱-质谱-质谱联用(LC/MS/MS)方法测定米索前列酸(MPA)的药代动力学参数。结果:阴道组和口服组的血浆MPA浓度达峰时间(Tmax)相似,但长于舌下组,3组间差异无统计学意义。舌下组MPA峰值浓度(Cmax)显著高于口服组和阴道组(P<0.001),但口服组和舌下组在给予米索前列醇2h后的MPA血浆浓度均已下降,且低于阴道组。阴道组和舌下组血药浓度时间曲线下面积(AUC720)相似,均高于口服组,3组间差异有统计学意义(P<0.05)。结论:国产米索前列醇阴道用药产生较高浓度的MPA,且在妊娠妇女体内维持较长时间,有较大的生物利用度,较口服和舌下用药可延长用药间隔,从而减少药物用量和降低临床副作用。

Plasma concentration of different routes of administration of domestic misoprostol

Objective：The plasma concentration of different routes of administration of domestic misoprostol was studied.Methods：A total of 26 women undergoing termination of early pregnancy by vacuum aspiration received 600ug of misoprostol by one of three routes：oral,vaginal,and sublingual.Venous blood samples were taken before and after the administration of misoprostol at 15min,30min,60 min,2 h,12 h（the last time in oral group was 3h after the misoprostol administration）.Misoprostol acid（MPA）was determined in serum samples using liquid chromatography/tandem mass spectrometry（LS/MS/MS）.Results：The time to peak concentration（Tmax）with regard to MPA was similar in both the oral and vaginal groups and longer than that in sublingual group,showing no significant differences.Sublingual misoprostol achieved the highest serum peak concentration（Cmax）of MPA and this was significantly higher than oral and vaginal groups（P〈0.001）,but the blood plasma concentrations of MPA at 2h in oral and sublingual groups were lower than that in the vaginal group.The area under the MPA concentration versus time curve（AUC）were similar between the vaginal and sublingual group,and a significant difference was found when the sublingual group compared to the oral group（P=0.023）.Conclusion：The peak plasma level of the domestic misoprostol after vaginal misoprostol is higher,and the MPA sustained a longer time and the bioavailability is also greater.Prolonged serum concentration could be dosed at longer interval,and lower dosage reduce the side effects when compared with oral and sublingual routes.