El-Baraky Iman A, Abbassi Maggie M, Marei Tarek A, Sabry Nirmeen A
Clinical Pharmacy Department, Faculty of Pharmacy.
Clinical Pharmacy Department, Faculty of Pharmacy.
J Cardiothorac Vasc Anesth. 2016 Aug;30(4):876-83. doi: 10.1053/j.jvca.2016.02.003. Epub 2016 Feb 11.
Because of the lack of data regarding the impact of obesity on propofol pharmacokinetics in patients undergoing cardiac surgery using hypothermic cardiopulmonary bypass (CPB), the authors sought to explore propofol pharmacokinetics and develop a predictive pharmacokinetic model that characterizes and predicts propofol pharmacokinetics in this population.
A prospective, observational study.
A teaching hospital.
The study comprised 17 obese and 17 control (nonobese) patients undergoing hypothermic CPB.
None.
Patients mainly underwent valve surgery. On initiation of hypothermic CPB (28°C-32°C), patients received a propofol (1%) bolus (1 mg/kg) immediately followed by a 2 mg/kg/h infusion. Blood samples were withdrawn at the following times: before dosing; 1, 3, 5, and 7 minutes after the propofol bolus dose; every 20 minutes during infusion; just before discontinuation of the infusion; and at 1, 3, 5, 7, 10, 20, 30, and 60 minutes after discontinuation of the infusion. The plasma propofol concentration was determined using high-performance liquid chromatography, and then data were imported into Monolix (Lixoft, Antony, France) for population pharmacokinetic modeling and pharmacokinetic parameters estimation. A 2-compartment pharmacokinetic model with age as a covariate on the peripheral volume of distribution (V2) best described the pooled data. The pooled data was internally evaluated successfully to describe and predict propofol pharmacokinetics in the addressed population. Propofol clearance, intercompartmental clearance, and central volume of distribution were 805 mL/min, 1140 mL/min and 18.8 L, respectively. V2 was calculated as 9.86×exp.(1.88×[age/40]) L.
Propofol pharmacokinetic parameters were similar in obese and nonobese patients undergoing hypothermic CPB. Age was the major determinant of propofol V2 in the obese population.
由于缺乏关于肥胖对接受低温体外循环（CPB）心脏手术患者丙泊酚药代动力学影响的数据，作者试图探索丙泊酚药代动力学，并建立一个预测药代动力学模型，以表征和预测该人群的丙泊酚药代动力学。
一项前瞻性观察性研究。
一家教学医院。
该研究包括17名肥胖患者和17名对照（非肥胖）患者，均接受低温CPB。
无。
患者主要接受瓣膜手术。在低温CPB（28°C - 32°C）开始时，患者立即接受丙泊酚（1%）负荷剂量（1 mg/kg），随后以2 mg/kg/h的速度输注。在以下时间点采集血样：给药前；丙泊酚负荷剂量后1、3、5和7分钟；输注期间每20分钟一次；输注即将停止前；输注停止后1、3、5、7、10、20、30和60分钟。使用高效液相色谱法测定血浆丙泊酚浓度，然后将数据导入Monolix（法国安东尼市Lixoft公司）进行群体药代动力学建模和药代动力学参数估计。一个将年龄作为外周分布容积（V2）协变量的二室药代动力学模型最能描述汇总数据。汇总数据在内部成功评估，以描述和预测目标人群的丙泊酚药代动力学。丙泊酚清除率、室间清除率和中央分布容积分别为805 mL/min、1140 mL/min和18.8 L。V2计算为9.86×exp.(1.88×[年龄/40]) L。
接受低温CPB的肥胖和非肥胖患者的丙泊酚药代动力学参数相似。年龄是肥胖人群中丙泊酚V2的主要决定因素。
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