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}) C t = C 0 + (C s s-C 0) (1-e-K t) 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.