Surgical Operation Department, Asahikawa Medical University Hospital, Asahikawa, Japan.
Department of Anesthesiology and Critical Care Medicine, Asahikawa Medical University, Asahikawa, Japan.
Ther Clin Risk Manag. 2015 Jan 17;11:107-14. doi: 10.2147/TCRM.S74867. eCollection 2015.
We previously determined the pharmacokinetic (PK) parameters of landiolol in healthy male volunteers and gynecological patients. In this study, we determined the PK parameters of landiolol in patients with peripheral arterial disease.
Eight patients scheduled to undergo peripheral arterial surgery were enrolled in the study. After inducing anesthesia, landiolol hydrochloride was administered at target plasma concentrations of 500 and 1,000 ng/mL for 30 minutes each. A total of 112 data points of plasma concentration were collected from the patients and used for the population PK analysis. A population PK model was developed using a nonlinear mixed-effect modeling software program (NONMEM).
The patients had markedly decreased heart rates at 2 minutes after initiation of landiolol hydrochloride administration; however, systolic blood pressures were lower than the baseline values at only five time points. The concentration time course of landiolol was best described by a two-compartment model with lag time. The estimates of PK parameters were as follows: total body clearance, 30.7 mL/min/kg; distribution volume of the central compartment, 65.0 mL/kg; intercompartmental clearance, 48.3 mL/min/kg; distribution volume of the peripheral compartment, 54.4 mL/kg; and lag time, 0.633 minutes. The predictive performance of this model was better than that of the previous model.
The PK parameters of landiolol were best described by a two-compartment model with lag time. Distribution volume of the central compartment and total body clearance of landiolol in patients with peripheral arterial disease were approximately 64% and 84% of those in healthy volunteers, respectively.
我们之前确定了健康男性志愿者和妇科患者中联苯洛尔的药代动力学（PK）参数。在这项研究中，我们确定了外周动脉疾病患者中联苯洛尔的 PK 参数。
本研究纳入了 8 名计划行外周动脉手术的患者。麻醉诱导后，以 500 和 1000ng/mL 的目标血浆浓度分别给予盐酸拉贝洛尔 30 分钟。从患者中采集了总共 112 个血浆浓度数据点，用于群体 PK 分析。使用非线性混合效应建模软件程序（NONMEM）开发了群体 PK 模型。
患者在开始给予盐酸拉贝洛尔后 2 分钟心率明显下降，但只有 5 个时间点的收缩压低于基线值。拉贝洛尔的浓度时间曲线最好用具有滞后时间的两室模型来描述。PK 参数的估计值如下：总体清除率为 30.7mL/min/kg；中央室分布容积为 65.0mL/kg；隔室清除率为 48.3mL/min/kg；外周室分布容积为 54.4mL/kg；滞后时间为 0.633 分钟。该模型的预测性能优于之前的模型。
拉贝洛尔的 PK 参数最好用具有滞后时间的两室模型来描述。外周动脉疾病患者的中央室分布容积和拉贝洛尔的总清除率分别约为健康志愿者的 64%和 84%。
