Pharmacokinetic and pharmacodynamic studies of L-dopa in rats. I. Pharmacokinetic analysis of L-dopa in rat plasma and striatum.
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 100 mg/kg. Plasma and striatum samples were obtained over 480 min (17 time points) from different group of animals and then assayed by HPLC-ECD. The endogenous L-dopa concentration in plasma before drug administration was 2.1 +/- 0.6 mg/l. The exogenous L-dopa concentration declined biexponentially with time after drug injection. The total clearance of exogenous L-dopa in plasma was 3.13(l/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.(ABSTRACT TRUNCATED AT 250 WORDS)
Sato
S
S
Department of Pharmaceutics, Niigata College of Pharmacy, Japan.
Koitabashi
T
T
Koshiro
A
A
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D007275:Injections, Intravenous; D007980:Levodopa / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D017072:Neostriatum / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D007980:Levodopa