A method to determine pharmacokinetic parameters based on andante constant-rate intravenous infusion

Abstract

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 ${C}_{t}={C}_{{0}}+{C}_{ss}-{C}_{{0}}\cdot 1-{e}^{-Kt}$ using the principle of calculus. Then, the method to determine the pharmacokinetic parameters was summed up. After collecting the blood drug concentration (C*t) -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**ss). Then, the half-life (t**1/2), apparent volume of distribution (V**d) and clearance rate (CL) were calculated based on the equations, t**1/2 = 0.693/K, V**d = (v/K)/C**ss and CL = v/C**ss*, respectively. In addition, an application example of cimetidine in a beagle dog was used to demonstrate the implementation process of the method.