Henthorn T K, Krejcie T C, Avram M J
Department of Anesthesia, Northwestern University Medical School, Chicago, IL 60611.
Clin Pharmacol Ther. 1992 Aug;52(2):190-6. doi: 10.1038/clpt.1992.129.
The relationship between cardiac output and the tissue distribution of alfentanil was investigated in seven healthy volunteers. Subjects were given 10 micrograms/kg alfentanil and 0.5 mg/kg indocyanine green. Arterial blood samples were obtained at baseline, 1 minute, every 1/2 minute until 5 minutes, and then every minute until 15 minutes after the drug injection was begun. Subsequent samples were collected to 6 hours. Cardiac output was measured continuously by use of thoracic bioimpedance. Alfentanil pharmacokinetics were modeled with both a standard three-compartment model and a four-compartmental model based in part on the two-compartmental pharmacokinetics of indocyanine green. The sum of intercompartmental clearances for both the three- and four-compartment models were significantly correlated with the measured cardiac outputs, r = 0.93 and r = 0.88, respectively. These findings indicate that the intercompartmental clearance (i.e., tissue distribution) of alfentanil is largely determined by cardiac output (i.e., tissue blood flow).
在七名健康志愿者身上研究了心输出量与阿芬太尼组织分布之间的关系。受试者接受了10微克/千克的阿芬太尼和0.5毫克/千克的吲哚菁绿。在基线、注射药物开始后1分钟、每1/2分钟直至5分钟，然后每1分钟直至15分钟采集动脉血样本。随后的样本采集至6小时。通过胸生物阻抗连续测量心输出量。阿芬太尼的药代动力学采用标准三室模型和四室模型进行建模，部分基于吲哚菁绿的二室药代动力学。三室模型和四室模型的室间清除率总和与测量的心输出量显著相关，分别为r = 0.93和r = 0.88。这些发现表明，阿芬太尼的室间清除率（即组织分布）在很大程度上由心输出量（即组织血流量）决定。
