Department of Pharmacology, Health Science Center, Xi'an Jiaotong University, Xi'an, China.
Sci Rep. 2017 Oct 16;7(1):13279. doi: 10.1038/s41598-017-13437-6.
On account of the disturbance from the distribution phase, the concentration-time curve of drugs cannot fully reflect the characteristics of elimination, and thus, it is difficult for present methods to obtain ideal pharmacokinetic parameters. This paper presents a method to determine pharmacokinetic parameters based on an andante constant-rate intravenous infusion. A mathematical model of the constant-rate intravenous infusion combined with the elimination of first-order kinetics was established. During infusion, the accumulation tendency of drugs was deduced as [Formula: see text] using the principle of calculus. Then, the method to determine the pharmacokinetic parameters was summed up. After collecting the blood drug concentration (C ) -time (t) data from a constant-rate (v) infusion period, an exponential regression analysis was conducted to obtain the elimination rate constant (K) and plateau concentration (C ). Then, the half-life (t ), apparent volume of distribution (V ) and clearance rate (CL) were calculated based on the equations, t = 0.693/K, V = (v/K)/C and CL = v/C , respectively. In addition, an application example of cimetidine in a beagle dog was used to demonstrate the implementation process of the method.
由于分布相的干扰，药物的浓度-时间曲线不能充分反映消除的特征，因此，目前的方法很难获得理想的药代动力学参数。本文提出了一种基于恒速静脉滴注的药代动力学参数确定方法。建立了恒速静脉滴注与一级动力学消除相结合的数学模型。在输注过程中，根据微积分原理推导出药物的蓄积趋势为[公式：见文本]。然后，总结了确定药代动力学参数的方法。在收集恒速（v）输注期的血药浓度（C）-时间（t）数据后，进行指数回归分析以获得消除率常数（K）和平台浓度（C）。然后，根据公式计算半衰期（t）、表观分布容积（V）和清除率（CL），分别为 t = 0.693/K、V = （v/K）/C 和 CL = v/C。此外，还用犬体内西咪替丁的应用实例说明了该方法的实施过程。
