Mertens M J, Vuyk J, Olofsen E, Bovill J G, Burm A G
Department of Anesthesiology, Leiden University Medical Center, The Netherlands.
Anesthesiology. 2001 Jun;94(6):949-57. doi: 10.1097/00000542-200106000-00006.
The influence of propofol on the pharmacokinetics of alfentanil is poorly understood. The authors therefore studied the effect of a pseudo-steady state concentration of propofol on the pharmacokinetics of alfentanil.
The pharmacokinetics of alfentanil was studied on two occasions in eight male volunteers in a randomized crossover manner with a 3-week interval. While breathing 30% O2 in air, 12.5 microg/kg intravenous alfentanil was given in 2 min, followed by 25 microg.kg(-1).h(-1) for 58 min (sessions A and B). During session B, a target controlled infusion of propofol (target concentration, 1.5 microg/ml) was given from 10 min before the start until 6 h after termination of the alfentanil infusion. Blood pressure, cardiac output, electrocardiogram, respiratory rate, oxygen saturation, and end-tidal carbon dioxide were monitored. Venous blood samples for determination of the plasma alfentanil concentration were collected until 6 h after termination of the alfentanil infusion. Nonlinear mixed-effects population pharmacokinetic models examining the influence of propofol and mean arterial pressure were constructed.
A three-compartment model, including a lag time accounting for the venous blood sampling, adequately described the concentration-time curves of alfentanil Propofol decreased the elimination clearance of alfentanil by 15%, rapid distribution clearance by 68%, slow distribution clearance by 51%, and lag time by 62%. Mean arterial pressure and systemic vascular resistance were significantly lower in the presence of propofol. Scaling the pharmacokinetic parameters to the mean arterial pressure instead of propofol improved the model.
Propofol alters the pharmacokinetics of alfentanil. Hemodynamic changes induced by propofol may have an important influence on the pharmacokinetics of alfentanil.
丙泊酚对阿芬太尼药代动力学的影响尚不清楚。因此，作者研究了丙泊酚伪稳态浓度对阿芬太尼药代动力学的影响。
8名男性志愿者以随机交叉方式，间隔3周分两次研究阿芬太尼的药代动力学。在吸入含30%氧气的空气时，于2分钟内静脉注射12.5微克/千克阿芬太尼，随后以25微克·千克-1·小时-1持续输注58分钟（A和B阶段）。在B阶段，从阿芬太尼输注开始前10分钟至输注结束后6小时给予丙泊酚靶控输注（靶浓度1.5微克/毫升）。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。在阿芬太尼输注结束后6小时内采集静脉血样以测定血浆阿芬太尼浓度。构建了检查丙泊酚和平均动脉压影响的非线性混合效应群体药代动力学模型。
三室模型，包括考虑静脉血采样的滞后时间，能充分描述阿芬太尼的浓度-时间曲线。丙泊酚使阿芬太尼的消除清除率降低15%，快速分布清除率降低68%，缓慢分布清除率降低51%，滞后时间降低62%。在使用丙泊酚时，平均动脉压和全身血管阻力显著降低。将药代动力学参数按平均动脉压而非丙泊酚进行标化可改善模型。
丙泊酚改变阿芬太尼的药代动力学。丙泊酚引起的血流动力学变化可能对阿芬太尼的药代动力学有重要影响。
