Klem C, Dasta J F, Reilley T E, Flancbaum L J
College of Pharmacy, Ohio State University, Columbus, OH.
Crit Care Med. 1994 Dec;22(12):1926-32.
To delineate the variability in the pharmacokinetics of dobutamine over time in an unstable critically ill adult surgical patient population concurrently receiving therapeutic interventions to optimize oxygen delivery and consumption variables.
Prospective study.
University hospital adult surgical intensive care unit.
Sixteen hemodynamically unstable adults (aged 18 to 84 yrs) requiring dobutamine for inotropic support.
None.
Samples for dobutamine serum concentration determination were collected at selected times during therapy, following at least 30 mins of a constant infusion rate and measured using high-performance liquid chromatography. Clearance and changes in clearance were calculated. A first-order pharmacokinetic model was validated by lack of dependence of dose on clearance and an established graphical method. Mean +/- SD infusion rate of dobutamine was 8.2 +/- 5.7 micrograms/kg/min (range 1.7 to 22.3), which resulted in a mean serum concentration of 214 +/- 183 ng/mL (range 15 to 759). The correlation between infusion rate and steady-state dobutamine concentration was r2 = .67. Variability in steady-state dobutamine concentration at various infusion rates was large. Clearance at initial pharmacokinetic analysis averaged 58.4 +/- 33.3 mL/kg/min (range 19 to 120). The percent change in calculated clearance varies from a 72% decrease to an 88% increase, with the greatest variability in clearance occurring during the first 24 hrs of therapy. There was little correlation between initial dobutamine clearance and weight (r2 = .10), net cumulative fluid balance before initiation of dobutamine (r2 < .01), age (r2 = .20), and estimated creatinine clearance (r2 = .09).
Dobutamine pharmacokinetics in adult critically ill patients is best described by a first-order model. Pathophysiologic factors may have an effect on the pharmacokinetics of dobutamine which appears to change over time. Both inter- and intrapatient variability in infusion rate administered and resultant serum concentrations were wide, suggesting that infusion rate should be guided by clinical end points rather than by predetermined values.
在同时接受优化氧输送和消耗变量的治疗干预措施的不稳定成年危重症外科患者群体中，描绘多巴酚丁胺药代动力学随时间的变化情况。
前瞻性研究。
大学医院成人外科重症监护病房。
16名血流动力学不稳定的成年人（年龄18至84岁），需要多巴酚丁胺进行强心支持。
无。
在治疗期间的选定时间采集用于测定多巴酚丁胺血清浓度的样本，在至少30分钟的恒定输注速率后，使用高效液相色谱法进行测量。计算清除率及清除率的变化。通过剂量对清除率的独立性缺乏以及既定的图形方法验证了一级药代动力学模型。多巴酚丁胺的平均±标准差输注速率为8.2±5.7微克/千克/分钟（范围1.7至22.3），导致平均血清浓度为214±183纳克/毫升（范围15至759）。输注速率与稳态多巴酚丁胺浓度之间的相关性为r2 = 0.67。不同输注速率下稳态多巴酚丁胺浓度的变异性很大。初始药代动力学分析时的清除率平均为58.4±33.3毫升/千克/分钟（范围19至120）。计算出的清除率的百分比变化从降低72%到增加88%不等，清除率的最大变异性出现在治疗的前24小时内。初始多巴酚丁胺清除率与体重（r2 = 0.10）、多巴酚丁胺开始使用前的净累积液体平衡（r2 < 0.01）、年龄（r2 = 0.20）和估计的肌酐清除率（r2 = 0.09）之间几乎没有相关性。
成人危重症患者的多巴酚丁胺药代动力学最好用一级模型来描述。病理生理因素可能对多巴酚丁胺的药代动力学有影响，且这种影响似乎随时间而变化。给药的输注速率以及由此产生的血清浓度在患者间和患者内的变异性都很大，这表明输注速率应以临床终点而非预定值为指导。
