Mertens Martijn J, Olofsen Erik, Burm Anton G L, Bovill James G, Vuyk Jaap
Department of Anesthesiology, Leiden University Medical Center, The Netherlands.
Anesthesiology. 2004 Apr;100(4):795-805. doi: 10.1097/00000542-200404000-00008.
The influence of alfentanil on the pharmacokinetics of propofol is poorly understood. Therefore, the authors studied the effect of a pseudo-steady state concentration of alfentanil on the pharmacokinetics of propofol.
The pharmacokinetics of propofol were studied on two occasions in eight male volunteers in a randomized crossover manner with a 3-week interval. While volunteers breathed 30% O2 in air, 1 mg/kg intravenous propofol was given in 1 min, followed by 3 mg.kg(-1).h(-1) for 59 min (sessions A and B). During session B, a target-controlled infusion of alfentanil (target concentration, 80 ng/ml) was given from 10 min before the start until 6 h after termination of the propofol infusion. Blood pressure, cardiac output, electrocardiogram, respiratory rate, oxygen saturation, and end-tidal carbon dioxide were monitored. Venous blood samples for determination of the blood propofol and plasma alfentanil concentration were collected until 6 h after termination of the propofol infusion. Nonlinear mixed-effects population pharmacokinetic models examining the influence of alfentanil and hemodynamic parameters on propofol pharmacokinetics were constructed.
A two-compartment model, including a lag time accounting for the venous blood sampling, adequately described the concentration-time curves of propofol. Alfentanil decreased the elimination clearance of propofol from 2.1 l/min to 1.9 l/min, the distribution clearance from 2.7 l/min to 2.0 l/min, and the peripheral volume of distribution from 179 l to 141 l. Scaling the pharmacokinetic parameters to cardiac output, heart rate, and plasma alfentanil concentration significantly improved the model.
Alfentanil alters the pharmacokinetics of propofol. Cardiac output and heart rate have an important influence on the pharmacokinetics of propofol.
阿芬太尼对丙泊酚药代动力学的影响尚不清楚。因此，作者研究了阿芬太尼伪稳态浓度对丙泊酚药代动力学的影响。
以随机交叉方式，在8名男性志愿者身上分两次研究丙泊酚的药代动力学，间隔3周。当志愿者吸入含30%氧气的空气时，在1分钟内静脉注射1mg/kg丙泊酚，随后以3mg·kg⁻¹·h⁻¹持续输注59分钟（A组和B组）。在B组中，从丙泊酚输注开始前10分钟至输注结束后6小时给予阿芬太尼靶控输注（靶浓度80ng/ml）。监测血压、心输出量、心电图、呼吸频率、血氧饱和度和呼气末二氧化碳。在丙泊酚输注结束后6小时内采集静脉血样，用于测定血丙泊酚和血浆阿芬太尼浓度。构建非线性混合效应群体药代动力学模型，研究阿芬太尼和血流动力学参数对丙泊酚药代动力学的影响。
一个包含考虑静脉血采样延迟时间的二室模型，能充分描述丙泊酚的浓度-时间曲线。阿芬太尼使丙泊酚的清除率从2.1升/分钟降至1.9升/分钟，分布清除率从2.7升/分钟降至2.0升/分钟，外周分布容积从179升降至141升。将药代动力学参数按心输出量、心率和血浆阿芬太尼浓度进行标化，可显著改善模型。
阿芬太尼改变丙泊酚的药代动力学。心输出量和心率对丙泊酚药代动力学有重要影响。
