pharmazentrum frankfurt/ZAFES, Institute of Clinical Pharmacology, J. W. Goethe-University Hospital, Frankfurt, Germany.
Clin Pharmacokinet. 2012 Oct 1;51(10):629-38. doi: 10.1007/s40262-012-0001-1.
Arterial blood sampling is necessary when drugs such as the fast-acting opioid analgesic remifentanil exhibit relevant differences between arterial and venous blood concentrations. Arterial cannulation is generally considered to be clinically safe and has thus become a standard procedure in pharmacokinetic-pharmacodynamic assessments. However, rare cases of arterial occlusions have to be considered in risk-benefit assessments of arterial sampling in pharmacokinetic studies, especially when including healthy volunteers. In an actual case, arterial occlusion requiring surgical repair was caused by a factor V Leiden thrombophilia associated genetic variant F5 1691G>A (rs6025) and aggravated by a hypoplastic radial artery. Neither risk factor had been identified prior to enrolment by routine laboratory tests such as the prothrombin time (international normalized ratio), partial thromboplastin time and the clinical Allen's test of arterial function. Re-assessment of the necessity of arterial sampling showed that none of the potential alternatives, target concentrations of computerized infusions or venous concentrations during non-steady-state and steady-state conditions could provide the arterial concentrations. Relying on venous concentrations may result in erroneous pharmacodynamic parameters. Accurate pharmacokinetic-pharmacodynamic studies relying on precisely measured blood concentrations require serial sampling techniques during both steady-state and non-steady-state conditions. However, as illustrated by the presented case, incidents involving the generally safe procedure of arterial sampling are possible, although rare. To further minimize the risks, screening of subjects for prothrombotic risks and careful assessment of the suitability of the artery should be considered in pharmacokinetic studies requiring arterial cannulation.
当快速作用的阿片类镇痛药瑞芬太尼等药物在动脉血和静脉血浓度上表现出相关差异时，需要进行动脉采血。一般认为动脉置管在临床上是安全的，因此已成为药代动力学-药效学评估的标准程序。然而，在药代动力学研究中进行动脉采血的风险-效益评估时，必须考虑到罕见的动脉闭塞病例，特别是在包括健康志愿者时。在一个实际案例中，由因子 V 莱顿血栓形成倾向遗传变异 F5 1691G>A(rs6025)引起的需要手术修复的动脉闭塞，并因发育不良的桡动脉而加重。在常规实验室检查（如凝血酶原时间[国际标准化比值]、部分凝血活酶时间和动脉功能的临床 Allen 试验）中，在入组前均未发现这两个危险因素。对动脉采血必要性的重新评估表明，潜在替代方案、计算机输注的目标浓度或非稳态和稳态条件下的静脉浓度都无法提供动脉浓度。依赖静脉浓度可能导致错误的药效学参数。依赖于精确测量的血液浓度的准确药代动力学-药效学研究需要在稳态和非稳态条件下进行连续采样技术。然而，正如所提出的案例所示，尽管罕见，但涉及一般安全的动脉采血程序的事件是可能发生的。为了进一步降低风险，在需要动脉置管的药代动力学研究中，应考虑对受试者进行血栓形成前风险的筛查，并仔细评估动脉的适宜性。
