注射用磷丙泊酚钠对QTc间期的影响及其血药浓度与QTc间期的关系

Effects of fospropofol disodium on corrected QT interval and relationship between its serum concentration and corrected QT interval

目的研究注射用磷丙泊酚钠单次静脉注射后健康成人校正后QT间期(QTc间期)的变化并探讨其及活性产物丙泊酚的血药浓度与QTc间期的关系。方法 30名健康青年受试者,男女各半,随机分为三组(n=10),分别给予注射用磷丙泊酚钠10、20、30 mg·kg-1单次静脉注射。于给药前后采集静脉血样测定血药浓度,记录给药前后共31个时点的标准12导联心电图,Fridericia公式计算QTc间期,观察QTc间期与性别的关系及给药前后的变化,分析磷丙泊酚钠和其代谢产物丙泊酚血药浓度与QTc间期的关系。结果给药前后女性受试者的QTc间期均大于男性受试者,差异均有显著意义(P<0.05)。给药后三个剂量组QTc间期均较基础值有不同程度的延长,最大值为492 ms,△QTc最大值为58 ms。三组QTc间期在给药后60 min时均已呈下降趋势,10 mg·kg-1组给药后35 min时基本恢复至基线值,其他两组仍长于基础值(P<0.05)。磷丙泊酚钠血药浓度与QTc间期无明显相关,丙泊酚血药浓度与QTc间期呈线性相关(r=0.460,P=0.005),QTc间期延长的效应存在滞后性。结论注射用磷丙泊酚钠单次静脉注射对健康青年受试者的QTc间期有一定延长作用,但该药可能并不会增加尖端扭转型室性心动过速的诱发几率。

AIM To study the variety of corrected QT interval （QTc） in healthy adults after a single bolus of fospropofol disodium and the relationship of QTc with serum level of fospropofol and propofol. METHODS Thirty healthy youth volunteers （male/female： 15/15） were randomly allocated into three groups （10 in each）. The participants in the group I , 11 and m were given a single bolus of fospropofol disodium 10, 20 and 30 mg·kg-1. The serum specimen was drawn and ECG was performed before and after the administration. QTc was calculated by the Fridericia formula. Values of the QTc change from baseline after administration and the gender difference in QTc were evaluated. The relationship between fospropofol disodium and its metabolites propofol blood concentration with QTc were analyzed. RESULTS The QTc of female participants before and after the administration were both greater than male subjects, differences were statistically significant （P 〈 0.05）. Compared with the baseline, QTc of each group was prolonged respectively. The maximum of QTc was 492 ms and the maximum of AQTc was 58 ms. The QTc of three groups had all declined at 60 min after the administration. The QTc of group I had recovered to baseline at 35 min after the administration while the other two groups had not （P 〈 0.05）. There was no significant relation between the QTc and fospropofol disodium serum concentration. But there was a significant linear relation between QTc and the serum concentration of propofol （r = 0.460, P = 0.005）. There were hysteresis effects of QTc prolongation in all groups. CONCLUSION A single bolus of fospropofol disodium may produce somewhat prolongation to QTc of healthy youth volunteers, but it may not increase the incidence rate of torsade de pointes.