Limitations and improvements of classical models of pharmacokinetics / 西安交通大学学报(医学版)

ABSTRACT

Compartment model and statistical moment model are important theories of pharmacokinetics. However, they have obvious limitations due to the influence of drug distribution. Sometimes, the demarcation point between the distribution phase and the elimination phase of the compartment model is difficult to determine, which results in inconvenience for its application. The nature of zero order moment, AUC of statistical moment model, is blood drug concentration, but not drug amount in the body. For drugs of two-compartment or multi-compartment models, the results reflect alterations in blood drug concentration, not necessarily changes in the amount of drug in the body. In the slow and steady intravenous drip, the drug distribution in the body is basically balanced, and the alteration of blood drug concentration can reflect the alteration of drug amount in the body. Over 5 half-life, the blood drug concentration basically reaches a stable status. And the alteration of the blood drug concentration only reflects the drug elimination. For first-order kinetic drugs, the elimination rate constant (K) can be calculated by linear regression according to the elimination rule (lnC=lnC0-Kt). And then, the half-life (t1/2), the amount of drug in the body, the apparent distribution volume (Vd), and the clearance rate (CL) can be calculated successively. During slow and constant velocity intravenous dripping, drug amount is proportional to blood drug concentration in the body. And there is an exponential relationship between the blood drug concentration and time [Ct=C0+(Css-C0) (1-e-Kt)]. The first-order exponential regression is performed between Ct and t to calculate elimination threshold concentration (C0), steady blood drug concentration (Css) and K. Then, t1/2, steady drug amount (Ass), Vd and CL are calculated. The distributed equilibrium model avoids the interference of drug distribution, and is closer to reality.