患者性别因素对丙泊酚药代动力学的影响

Effects of gender on pharmacokinetics of propofol

目的评价患者性别因素对丙泊酚药代动力学的影响。方法择期拟行胃肠道肿瘤手术患者20例，年龄42～59岁，体重46～76kg，ASA分级Ⅰ或Ⅱ级，按不同性别分为2组（n=10）：男性组和女性组。均采用静吸复合全身麻醉。麻醉诱导：静脉注射2％丙泊酚2mg／kg，瑞芬太尼1．5μg／kg，氯化琥珀胆碱1．5mg／kg，经口气管插管并行机械通气；麻醉维持：吸入1％-2％异氟醚和N2O：O2（1：1）混合气体，静脉输注瑞芬太尼0．2～0．3μg／kg，术中间断静脉注射阿曲库铵维持肌松。于丙泊酚给药前和给药后1、2、3、4、6、10、15、30、45、60、90、120、180、240、360和720min时抽取中心静脉血样3ml，采用高效液相色谱．荧光检测法测定血浆丙泊酚浓度，绘制血药浓度-时间曲线，计算药代动力学参数。结果女性组单次静脉注射丙泊酚10min内各时点血药浓度明显低于男性组（P〈0．05），2组患者丙泊酚的血药浓度．时间曲线均符合三房室开放模型；女性组丙泊酚的中央室分布容积和清除率明显大于男性组（P〈0．05）。结论静脉注射丙泊酚后，女性患者血药浓度低于男性，中央室分布容积和清除率大于男性，提示性别因素对丙泊酚的药代动力学有明显影响。

Objective To evaluate the effects of gender on the pharmacokinetics of propofol in patients. Methods Twenty ASA physical status Ⅰ or Ⅱ patients of both sexes （ 10 male, 10 female）, aged 42-59 yr, weighing 46-76 kg, scheduled for elective surgery for gastrointestinal cancer, were randomly divided into 2 gender groups （ n = 10 each） ： male group and female group. Combined intravenous-inhalational anesthesia was performed during surgery. Anesthesia was induced with iv injection of 2% propofol 2 mg/kg, remifentanil i .5 μg/kg, and suxamethonium chloride 1.5 mg/kg. The patients were tracheally intubated and mechanically ventilated. Anesthe- sia was maintained with inhalation of the mixture of 1% -2 % isoflurane and nitrous oxide （ N2O ：O2 = 1 ： 1 ）, iv in- fusion of remifentanil 0.2-0.3 μg/kg and intermittent iv boluses of atracurium. Blood samples were taken from the central vein before propofol administration, and at 1, 2, 3, 4, 6, 10, 15, 30, 45, 60, 90, 120, 180, 240, 360 and 720 min after propofol administration for determination of the plasma concentration of propofol by high-perfor- mance liquid ehromatography. The blood concentration-time curve of propofol was drawn and the pharmacokinetic parameters were calculated. Results The blood concentrations of propofol were significantly lower at each time points within 10 min after administration of the single bolus of propofol in female group than in male group （ P 〈 0.05）. The blood concentration-time curves of propofol were fitted to a three-compartment open model in the 2groups. The central volume of distribution and clearance rate were significantly larger in female patients than in male patients （ P 〈 0.05）. Conclusion After iv injection of propofol, the blood concentration of propofol is low- er, and the central volume of distribution and clearance rate are larger in female than in male, suggesting that gen- der has significant effect on pharmacokinetics of propofol.