摘要：The purpose of this investigation was to quantitatively describe the pharmacokinetics of exogenous and endogenous L-dopa in plasma and the striatum using a basic physiological model, and to determine the apparent metabolism clearance from L-dopa to dopamine in the striatum. Male Wistar rats were used in this study. The time courses of L-dopa concentrations in plasma and the striatum were determined before and after the rapid i. v. injection of 10, 50 and 100mg/kg. Plasma and striatum samples were obtained over 480min (17 time points) from different group of animals and the assayed by HPLC-ECD. The endogenous L-dopa concentration in plasma before drug administration was 2.1±0.6mg/I. The exogenous L-dopa concentration declined biexponentially with time after drug injection. The total clearance of exogenous L-dopa in plasma was 3.13 (I/h)/kg. The production rate constant of endogenous L-dopa in plasma was 6.59 (mg/h)/kg. The value of the production rate constant of endogenous L-dopa in plasma could be calculated by the multiplication of the total clearance of L-dopa and the endogenous L-dopa concentration in plasma before drug injection. The pharmacokinetics of endogenous and exogenous L-dopa in plasma could be described quantitatively by a two compartment model which included the production rate constant of endogenous L-dopa. The time course of L-dopa concentrations in the striatum was analyzed on a hybrid model in which the striatum compartment is independently connected with the plasma compartment by the apparent diffusion clearance. The striatum compartment has two apparent first-order clearance terms, one from the plasma to the striatum, the other from the striatum to the outside of the striatum, including the metabolism clearance from L-dopa to dopamine in the striatum. The time course of L-dopa concentration in the striatum could be described by the basic physiological model, and the apparent metabolism clearance from L-dopa to dopamine in the striatum could be determined by the basic physiological model.
