Egan T D, Huizinga B, Gupta S K, Jaarsma R L, Sperry R J, Yee J B, Muir K T
Department of Anesthesiology, University of Utah Health Sciences Center in Salt Lake City, 84132, USA.
Anesthesiology. 1998 Sep;89(3):562-73. doi: 10.1097/00000542-199809000-00004.
Remifentanil is a short-acting opioid whose pharmacokinetics have been characterized in detail. However, the impact of obesity on remifentanil pharmacokinetics has not been specifically examined. The goal of this study was to investigate the influence of body weight on remifentanil pharmacokinetics.
Twelve obese and 12 matched lean subjects undergoing elective surgery received a 1-min remifentanil infusion after induction of anesthesia. Arterial blood samples were collected for determination of remifentanil blood concentrations. Each subject's pharmacokinetic parameters were estimated by fitting a two-compartment model to the concentration versus time curves. Nonlinear mixed-effects population models examining the influence of lean body mass (LBM) and total body weight (TBW) were also constructed. Clinical simulations using the final population model were performed.
The obese patient cohort reached substantially higher remifentanil concentrations. The individual pharmacokinetic parameters of a two-compartment model were not significantly different between the obese versus lean cohorts (unless normalized to TBW). The final population model scaled central clearance and the central and peripheral distribution volumes to LBM. The simulations illustrated that remifentanil pharmacokinetics are not grossly different in obese versus lean subjects and that TBW based dosing in obese patients can result in excessively high remifentanil concentrations.
The essential findings of the study are that remifentanil's pharmacokinetics are not appreciably different in obese versus lean subjects and that remifentanil pharmacokinetic parameters are therefore more closely related to LBM than to TBW. Clinically this means that remifentanil dosing regimens should be based on ideal body weight (or LBM) and not TBW.
瑞芬太尼是一种短效阿片类药物，其药代动力学已得到详细描述。然而，肥胖对瑞芬太尼药代动力学的影响尚未得到专门研究。本研究的目的是调查体重对瑞芬太尼药代动力学的影响。
12名肥胖受试者和12名相匹配的瘦体重受试者接受择期手术，麻醉诱导后接受1分钟的瑞芬太尼输注。采集动脉血样以测定瑞芬太尼血药浓度。通过将二室模型拟合到浓度-时间曲线来估计每个受试者的药代动力学参数。还构建了检查瘦体重（LBM）和总体重（TBW）影响的非线性混合效应群体模型。使用最终群体模型进行临床模拟。
肥胖患者队列达到的瑞芬太尼浓度显著更高。肥胖组与瘦体重组之间二室模型的个体药代动力学参数无显著差异（除非按TBW进行标准化）。最终群体模型将中央清除率以及中央和外周分布容积按LBM进行标化。模拟结果表明，肥胖受试者与瘦体重受试者的瑞芬太尼药代动力学没有明显差异，并且肥胖患者基于TBW的给药可能导致瑞芬太尼浓度过高。
该研究的主要发现是，肥胖受试者与瘦体重受试者的瑞芬太尼药代动力学没有明显差异，因此瑞芬太尼药代动力学参数与LBM的关系比与TBW的关系更密切。临床上这意味着瑞芬太尼给药方案应基于理想体重（或LBM）而非TBW。
