Persson M P, Nilsson A, Hartvig P
Department of Biopharmaceutics and Pharmacokinetics, University of Uppsala, Sweden.
Br J Anaesth. 1988 Jun;60(7):755-61. doi: 10.1093/bja/60.7.755.
Alfentanil was administered, together with midazolam, as part of a total i.v. anaesthetic technique. The pharmacokinetics of alfentanil were determined in 10 female patients undergoing lower abdominal surgery. The dose regimen of alfentanil, based on simulation studies, consisted of a two-stage infusion following an initial bolus dose. The kinetics of alfentanil were described by a linear two-compartment open model. The total plasma clearance ranged between 93 and 431 ml min-1 (mean 249 ml min-1). The apparent volume of distribution at steady-state ranged between 0.27 and 0.64 litre kg-1 (mean 0.44 litre kg-1). The apparent volume of distribution (Vd beta) was 0.58 litre kg-1, resulting in a terminal half-life of 112 min. Alfentanil concentrations at the time of extubation and postoperative analgesic requirements were also monitored. Good correlation between respiratory depression and plasma alfentanil concentration was found. Neither lower abdominal surgery nor the simultaneous administration of midazolam seemed to affect the kinetics of alfentanil as compared with results from studies in healthy volunteers. The short half-life of alfentanil, resulting from a small volume of distribution, makes it suitable as part of a total i.v. technique. Consideration must be paid, however, to interindividual differences in the pharmacodynamic response and in plasma clearance.
阿芬太尼与咪达唑仑一起作为全静脉麻醉技术的一部分给药。在10名接受下腹部手术的女性患者中测定了阿芬太尼的药代动力学。基于模拟研究,阿芬太尼的给药方案包括在初始推注剂量后进行两阶段输注。阿芬太尼的动力学由线性二室开放模型描述。总血浆清除率在93至431 ml·min⁻¹之间(平均249 ml·min⁻¹)。稳态时的表观分布容积在0.27至0.64 L·kg⁻¹之间(平均0.44 L·kg⁻¹)。表观分布容积(Vdβ)为0.58 L·kg⁻¹,终末半衰期为112分钟。还监测了拔管时的阿芬太尼浓度和术后镇痛需求。发现呼吸抑制与血浆阿芬太尼浓度之间有良好的相关性。与健康志愿者的研究结果相比,下腹部手术和同时给予咪达唑仑似乎都不影响阿芬太尼的动力学。阿芬太尼分布容积小导致半衰期短,使其适合作为全静脉技术的一部分。然而,必须考虑药效学反应和血浆清除率的个体差异。