QT 间期与性别给药前男 性 QTc 间期为 (403 ±11) ms, 女性为 (415 ± 20) ms, 差异非常显著administration and the gender difference in QTc were evaluated. The relationship between fospropofol disodiumand its metabolites propofol blood concentration with QTc were analyzed. RESULTSThe QTc of femaleparticipants before and after the administration were both greater than male subjects,differences werestatistically 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 △QTc was 58 ms. The QTc of three groups had alldeclined at 60 min after the administration. The QTc of group Ⅰ had recovered to baseline at 35 min after theadministration while the other two groups had not (P < 0.05) . There was no significant relation between the QTcand fospropofol disodium serum concentration. But there was a significant linear relation between QTc and theserum concentration of propofol (r = 0.460, P = 0.005) . There were hysteresis effects of QTc prolongation in allgroups. CONCLUSIONA single bolus of fospropofol disodium may produce somewhat prolongation to QTc ofhealthy youth volunteers, but it may not increase the incidence rate of torsade de pointes.131·· 中国新药与临床杂志(Chin J New Drugs Clin Rem),2013 年 2 月 , 第 32 卷 第 2 期(P < 0.01); 给药后男性和女性的 QTc 间期分别为(416 ± 17) 和 (432 ± 20) ms, 女性 QTc 间期亦显著长于男性 (P < 0.01)。QT 间期延长时点及程度与基线值相比, 三组在给药后 60 min 内 QTc 间期都有不同 程度的延长,且在给药后 60 min 时均已 呈下降趋势, 见图 1。Ⅰ 组和Ⅱ 组 QTc 间期给药后 4 min 分别为 (416 ±21)、 (424 ±18) ms, 出 现显著延长, 与基础值相比差异非常显著 (P < 0.01) , 而Ⅲ 组 QTc 间期给药后 2 min 即出现显著延长 [(415 ± 12) ms, 与基础值相比 P < 0.01]。 给药后 35 min 时, Ⅰ 组 QTc间期基本恢复至基线值 [(416 ± 24) ms, 与基础值相比 P > 0.05], 而Ⅱ 组及Ⅲ 组在给药后 60 min分别为 (423 ± 16)、 (423 ± 14) ms, 仍高于基线值 (P < 0.01)。 三组各时点 QTc 间期均值均未超过正常值上限 (男性 450 ms, 女性 470 ms), QTc间期最大值为 492 ms, 发生在Ⅱ 组一例女性给药后 9 min 时, 呈一过性, 于给药后 10 min 时下降至 463 ms, 于给药后 60 min 恢复到基线水平。 所有受试者中的△QTc 最大值为 58 ms。血药浓度与 QTc 间期磷丙泊酚钠血药浓度约在给药后 4 min 达到峰值, 丙泊酚的血药浓度在给药后 11 min 达到峰值, QTc 间期随给药剂量升高达到峰值的时间逐渐延后, Ⅰ 、 Ⅱ 、 Ⅲ 组分别为给药后 13、 19、 35 min, 见表 2、 表 3。磷丙 泊 酚 钠 血 药 浓 度 与 QTc 间 期 无 相 关 性(r = 0.055, P = 0.752), 散点图略。 丙泊酚血药浓度与 QTc 间期相关, QTc 间期随丙泊 酚血药浓度的 升高而增 大 (r = 0.460, P = 0.005) , 见 图 2。各组 QTc 间 期均随丙泊 酚血药浓度增大而增大,但最大效应滞后于血药浓度峰值, 三组均有逆时针方向的滞后环, 见图 3。其他心血管事件三组均未出 现尖端扭转型室性心动过速、 心室纤颤及心脏骤停。 共 23 例受试者出现了 7 种心电图相关的不良反应, 分别为 QT 间期延长、 T 波改变、 窦性心动过缓、 窦性心动过速、 传导障碍、 胸导联低电压、 短 PR 间期, 但均持续时间短, 未出现临床症状。表 1三组不同剂量磷丙泊酚钠健康受试者的人口学资料n = 10指标10 mg ·kg-1组5∶520 mg ·kg-1组5∶530 mg ·kg-1组5∶5性别/例男∶女年龄/岁22.6 ± 2.258.8 ± 8.722.7 ± 2.456.2 ± 7.622.5 ± 1.758.8 ± 6.1体重/kg体重指数/kg ·m-2QTc 间期/ms三组比较, 经方差分析或 χ2检验: 均 P > 0.0521.3 ± 1.420.6 ± 1.520.8 ± 1.3408 ± 14413 ± 20405 ± 17表 3给药后三组丙泊酚血药浓度与 QTc 间期均值n = 10时间/min血药浓度/ng ·mL-110 mg ·kg-120 mg ·kg-1QTc 间期/ms20 mg ·kg-1组组30 mg ·kg-1组10 mg ·kg-1组409组41530 mg ·kg-1组41016502834741 04188941141741746591 4941 90041642441958001 7593 05941442141471 0052 3154 04441842742191 1662 5924 422419431423111 2872 6324 463422433420151 1392 3864 229423440423307661 6422 532415439429407001 4402 082410432427506601 4201 850412426430606131 3801 922408423423表 2给药后三组磷丙泊酚钠血药浓度与 QTc 间期均值n = 10时间/min血药浓度/ng ·mL-110 mg ·kg-1组QTc 间期/ms20 mg ·kg-1组20 mg ·kg-1组30 mg ·kg-1组10 mg ·kg-1组30 mg ·kg-1组1261517409415410315325521841141741741702883944164244195151279348414421414713023129441842742199919324641943142311741431674224334201551100118423440423302054644154394294011333841043242750621264124264306041519408423423132