Nigrovic Vladimir, Proost Johannes H, Amann Anton, Bhatt Shashi B
Department of Anesthesiology, Medical University of Ohio, Toledo, OH, USA.
Theor Biol Med Model. 2005 Oct 3;2:41. doi: 10.1186/1742-4682-2-41.
The study examines the role of the volume of the effect compartment in simulations of neuromuscular block (NMB) produced by nondepolarizing muscle relaxants.
The molar amount of the postsynaptic receptors at the motor end plates in muscle was assumed constant; the apparent receptor concentration in the effect compartment is the ratio of this amount and the volume arbitrarily assigned to the effect compartment. The muscle relaxants were postulated to diffuse between the central and the effect compartment and to bind to the postsynaptic receptors. NMB was calculated from the free concentration of the muscle relaxant in the effect compartment.
The simulations suggest that the time profiles of NMB and the derived pharmacokinetic and pharmacodynamic variables are dependent on the apparent receptor concentration in the effect compartment. For small, but not for large, volumes, times to peak submaximal NMB are projected to depend on the magnitude of NMB and on the binding affinities.
An experimental design to estimate the volume of the effect compartment is suggested.
本研究探讨效应室容积在非去极化肌松药产生的神经肌肉阻滞（NMB）模拟中的作用。
假设肌肉运动终板处突触后受体的摩尔量恒定；效应室中表观受体浓度为此量与任意指定给效应室的容积之比。假定肌松药在中央室和效应室之间扩散并与突触后受体结合。NMB由效应室中肌松药的游离浓度计算得出。
模拟结果表明，NMB的时间曲线以及推导的药代动力学和药效学变量取决于效应室中的表观受体浓度。对于小容积而非大容积，次最大NMB峰值时间预计取决于NMB的大小和结合亲和力。
提出了一种估计效应室容积的实验设计。
