Department of Outcomes Research-E30, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Br J Anaesth. 2012 May;108(5):784-91. doi: 10.1093/bja/aer517. Epub 2012 Feb 13.
Nefopam is a non-opioid, non-steroidal, centrally acting analgesic which has an opioid-sparing effect. It also reduces the threshold (triggering core temperature) for shivering without causing sedation or respiratory depression. The drug is therefore useful as both an analgesic and to facilitate induction of therapeutic hypothermia. However, compartmental pharmacokinetics during hypothermia are lacking for nefopam.
We conducted a prospective, randomized, blinded study in eight volunteers. On two different occasions, one of two nefopam concentrations was administered and more than 30 arterial blood samples were gathered during 12 h. Plasma concentrations were determined using gas chromatography/mass spectrometry to investigate the pharmacokinetics of nefopam with non-linear mixed-effect modelling.
A two-compartment mammillary model with moderate inter-individual variability and inter-occasional variability independent of covariates was found to best describe the data [mean (SE): V(1)=24.13 (2.8) litre; V(2)=183.34 (13.5) litre; Cl(el)=0.54 (0.07) litre min(-1); Cl(dist)=2.84 (0.42) litre min(-1)].
The compartmental data set describing a two-compartment model was determined and could be implemented to drive automated pumps. Thus, work load could be distributed to a pump establishing and maintaining any desired plasma concentration deemed necessary for a treatment with therapeutical hypothermia.
奈福泮是一种非阿片类、非甾体类、中枢作用的镇痛药，具有阿片类药物的节省作用。它还降低了寒战的阈值（触发核心体温）而不引起镇静或呼吸抑制。因此，该药物既可用作镇痛药，也可用于促进治疗性低温的诱导。然而，奈福泮在低温时的房室药代动力学尚不清楚。
我们在 8 名志愿者中进行了一项前瞻性、随机、双盲研究。在两种不同情况下，给予两种奈福泮浓度中的一种，并在 12 小时内采集了 30 多次动脉血样。使用气相色谱/质谱法测定血浆浓度，通过非线性混合效应模型研究奈福泮的药代动力学。
发现一个具有中度个体间变异性和与协变量无关的偶发性变异性的两室乳突模型最能描述数据[平均（SE）：V(1)=24.13（2.8）升；V(2)=183.34（13.5）升；Cl(el)=0.54（0.07）升分钟(-1)；Cl(dist)=2.84（0.42）升分钟(-1)]。
确定了描述两室模型的房室数据集，并可将其用于驱动自动泵。因此，可以将工作量分配给一个泵，该泵可以建立和维持任何认为对治疗性低温所需的理想血浆浓度。
