Pharmacokinetic variability and therapeutic drug monitoring actions at steady state.
Pharmacokinetic variability and therapeutic drug monitoring actions at steady state.
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稳态下的药代动力学变异性和治疗药物监测作用。
DOI：
10.1023/a:1007573001055
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发表时间：
2000
影响因子：
3.7
通讯作者：
Ramanathan,M
中科院分区：
文献类型：
--
作者：
Ramanathan,M
目的。开发治疗药物监测的数学模型，并评估纠正措施的强度和药物浓度接近目标值之间的动力学关系。方法。使用了一个数学模型，该模型简洁地解释了纠正措施和药代动力学固有的变异性。结果。使用药物普鲁卡因酰胺稳态浓度的实验数据测试了变异项的有效性。监测过程到目标值的方法遵循指数动力学，并导出了随时间和各种给药参数变化的依赖性的分析表达式。药物浓度的方差主要取决于单个无量纲参数，该参数包含治疗校正动作的速率常数和描述方差率的系数。当治疗纠正措施的速率常数小于该临界值时，方差无限增加。结论。从剂量的角度来看，药物浓度的巨大差异是不希望的，因为一些患者会用药过量或剂量不足。由于确定性模型无法提供药物浓度分布函数矩的解析解，因此随机模型可用于为治疗方案的设计提供有用的见解。
Purpose. To develop a mathematical model for therapeutic drugmonitoring and to assess the kinetic relationships between the intensity ofcorrective action and the approach of drug concentrations to targetvalues.Methods. A mathematical model that succinctly accounts for thecorrective actions and the variability inherent in the pharmacokineticswas used.Results. The validity of the variability term was tested usingexperimental data for steady state concentrations of the drug procainamide.The approach of the monitored process to the target value followedexponential kinetics and an analytical expression for dependence thevariance with time and various dosing parameters was derived. Thevariance of the drug concentration depends critically on a singlenon-dimensional parameter containing the rate constant for the therapeuticcorrective actions and a coefficient describing the variance rate. Whenthe rate constant for the therapeutic corrective actions was less thanthis critical value, the variance increased indefinitely.Conclusions. From a dosing standpoint, large variances in drugconcentrations are undesirable because some patients will be overdosedor underdosed. Since deterministic models cannot provide analyticalsolutions for the moments of drug concentration distribution functions,stochastic models can be used to provide useful insights into the designof therapeutic regimens.