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 (Ct) -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 (Css). Then, the half-life (t1/2), apparent volume of distribution (Vd) and clearance rate (CL) were calculated based on the equations, t1/2 = 0.693/K, Vd = (v/K)/Css and CL = v/Css, respectively. In addition, an application example of cimetidine in a beagle dog was used to demonstrate the implementation process of the method.
Highlights
After collecting the blood drug concentration (Ct) -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 (Css)
In the non-compartmental analysis, the determination of K and t1/2 are based on the terminal elimination phase
In the non-compartmental analysis, clearance rate (CL) is estimated through the area under the curve (AUC), which is an interim parameter that is related to the entire concentration-time curve, in which the unbalanced distribution phase is included
Summary
After collecting the blood drug concentration (Ct) -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 (Css). The noncompartmental analysis is similar to kinetic analyses used in other scientific disciplines, such as chemical kinetics and chromatographic theory, both of which are analyzed basing on statistical moments principles.[1] The noncompartmental method evaluates the exposure of a drug by estimating the area under the curve (AUC) and the moment curve (AUMC) of a drug concentration-time graph, which is more versatile in that it relies very little on the compartmental model or the in vivo process of the drugs. The number of compartments for the same drug will not be unique when the administration route or the sample schedule is different.[2] The noncompartmental method estimates the elimination rate constant and half-life by performing a linear regression of the logarithmic drug concentration-time data in the terminal phase.[3,4] the terminal phase is only a part of the elimination phase. Its ultimate cause is the interference of the distribution phase, especially for drugs of the bi- or multi-compartment model, and it is difficult to figure the pure elimination phase out to determine the pharmacokinetic parameters
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