Fisher D M, Wright P M
Department of Anesthesia, University of California, San Francisco 94143-0648, USA.
Anesthesiology. 1997 Mar;86(3):567-75. doi: 10.1097/00000542-199703000-00008.
The traditional approach to pharmacokinetic/ pharmacodynamic modeling of muscle relaxants requires sampling of plasma to determine drug concentrations. The authors recently proposed that certain pharmacodynamic characteristics (IR50, the steady-state infusion rate to maintain 50% twitch depression; keo, the rate constant for equilibration between plasma concentration and effect; and gamma, the Hill factor describing sigmoidicity of the concentration-effect relation) could be estimated without plasma concentration data. Here estimates for IR50, keo, and gamma determined with and without plasma concentration data are compared.
Six volunteers were given 15-60 micrograms/kg vecuronium on each of two occasions during anesthesia with propofol. Mechanical responses to train-of-four stimulation were measured at the adductor pollicis and at the laryngeal adductors. Various pharmacokinetic models accounting for the presence and potency of vecuronium's 3-desacetyl metabolite and a sigmoid e-max pharmacodynamic model were fit to the resulting plasma concentration and effect (adductor pollicis and laryngeal adductors) data to determine IR50 keo, and gamma for each effect. One model related dose to effect without plasma concentration data.
Values for IR50(adductor pollicis), IR50(laryngeal adductors), gamma (adductor pollicis), and gamma (laryngeal adductors) were similar when determined with and without plasma concentration values. Values for keo (adductor pollicis) and keo (laryngeal adductors) were larger when determined without plasma concentration values compared with those determined with these values; however, the ratio of keo (adductor pollicis) to keo(laryngeal adductors) was similar when determined with and without plasma concentration values.
Certain pharmacodynamic parameters were estimated accurately in the absence of plasma concentration values. This suggests limited utility for plasma concentration data under conditions similar to those of the present study.
肌肉松弛剂药代动力学/药效动力学建模的传统方法需要采集血浆样本以测定药物浓度。作者最近提出，某些药效学特征（IR50，维持50%颤搐抑制的稳态输注速率；keo，血浆浓度与效应之间平衡的速率常数；以及γ，描述浓度-效应关系S形曲线的希尔系数）无需血浆浓度数据即可估算。在此，对有和无血浆浓度数据时测定的IR50、keo和γ的估算值进行比较。
6名志愿者在丙泊酚麻醉期间分两次接受15 - 60微克/千克维库溴铵。在拇收肌和喉内收肌测量对四个成串刺激的机械反应。将考虑维库溴铵3 - 去乙酰代谢产物的存在和效力的各种药代动力学模型以及S形e - max药效动力学模型拟合到所得的血浆浓度和效应（拇收肌和喉内收肌）数据，以确定每种效应的IR50、keo和γ。一个模型在无血浆浓度数据的情况下将剂量与效应相关联。
有和无血浆浓度值时测定的IR50（拇收肌）、IR50（喉内收肌）、γ（拇收肌）和γ（喉内收肌）值相似。与有血浆浓度值时测定的相比，无血浆浓度值时测定的keo（拇收肌）和keo（喉内收肌）值更大；然而，有和无血浆浓度值时测定的keo（拇收肌）与keo（喉内收肌）的比值相似。
在无血浆浓度值的情况下，某些药效学参数能被准确估算。这表明在与本研究类似的条件下，血浆浓度数据的实用性有限。
