Manfio J L, Santos L M, Carmona M J C, Dos Santos M B, Santos S Rcj
Laboratory of Clinical Pharmacology and Therapeutics, Pharmacy Department, School of Pharmaceutical Sciences, University of Sao Paulo - Sao Paulo (SP), Brazil.
Drug Res (Stuttg). 2013 Oct;63(10):495-500. doi: 10.1055/s-0033-1343470. Epub 2013 Jun 18.
Plasma monitoring and pharmacokinetic assessment are important tools used in therapeutic control. Sufentanil is responsible for the hemodynamic stabilization of patients, providing better suppression of the neuroendocrine response compared to its analogue fentanyl. This study aims to use the plasma monitoring of sufentanil in patients undergoing cardiac surgery with extracorporeal circulation (ECC, group 1) or without ECC (group 2) to assess the pharmacokinetics of the compound.The 42 patients in this study received 0.5 μg/kg of sufentanil through bolus injection followed by a maintenance infusion of 0.5 μg/kg.h. Serial blood samples were collected during the post induction intraoperative period and during the postoperative period until 36 h after sufentanil administration. The plasma concentrations were determined by a validated method utilizing liquid chromatography coupled to mass spectrometry. The pharmacokinetic modeling was performed using a 3-compartment model fit.The surgical patients included in the protocol were adults of both genders, with 30 patients in the ECC group and 12 in the group without ECC. The plasma concentrations obtained were significantly different between the 2 groups. During the extracorporeal circulation procedure, intense fluctuations were observed in the sufentanil plasma concentrations. Compared with the results of group 2, the ECC procedure reduced the terminal or gamma half-life from 36.35 ± 6.37 h to 23.25 ± 2.75 h in group 1. In addition, the ECC procedure promoted higher fluctuations in the sufentanil plasma concentrations without causing alterations in the area under the curve, distribution volume, clearance or the distributional (alpha) and rapid elimination (beta) half-lives (t1/2α and t1/2β, respectively).
血浆监测和药代动力学评估是治疗控制中使用的重要工具。舒芬太尼负责患者的血流动力学稳定，与它的类似物芬太尼相比，能更好地抑制神经内分泌反应。本研究旨在通过对接受体外循环心脏手术（ECC，第1组）或非体外循环心脏手术（第2组）患者的舒芬太尼进行血浆监测，来评估该化合物的药代动力学。本研究中的42例患者通过静脉推注接受了0.5μg/kg的舒芬太尼，随后以0.5μg/kg·h的速度持续输注。在诱导后术中及术后直至舒芬太尼给药后36小时期间采集系列血样。血浆浓度通过一种经过验证的液相色谱-质谱联用方法测定。药代动力学建模采用三室模型拟合。纳入方案的手术患者为成年男女，ECC组有30例患者，非ECC组有12例患者。两组获得的血浆浓度存在显著差异。在体外循环过程中，观察到舒芬太尼血浆浓度有剧烈波动。与第2组结果相比，ECC手术使第1组的终末或γ半衰期从36.35±6.37小时缩短至23.25±2.75小时。此外，ECC手术使舒芬太尼血浆浓度波动更大，但未导致曲线下面积、分布容积、清除率或分布（α）和快速消除（β）半衰期（分别为t1/2α和t1/2β）发生改变。
