Chronic Administration Does Not Alter the Pharmacokinetic Profile of L-Dopa in the Rat

Abstract

Abstract Chronic administration of L-dopa (200 mg kg−1 day−1 for 12 months) plus carbidopa (25 mg kg−1 day−1) or carbidopa (25 mg kg−1 day−1) alone did not alter the t½, AUC0–∞ k10, k12, k21, CLp or Vdss of L-dopa following intra-aortic (i.a.) administration (50 mg kg−1) alone or after carbidopa (25 mg kg−1, i.p.) pretreatment, or the t½, AUC0–∞, tmax or the bioavailability (F) of L-dopa (50 mg kg−1) administered orally, alone or after acute pretreatment with carbidopa (25 mg kg−1 i.p.). The peripheral metabolism of l-dopa was unaltered by chronic administration of L-dopa plus carbidopa or carbidopa alone as measured by unaltered AUC0·360 min for 3-O-methyldopa, dopamine, DOPAC or homovanillic acid in the plasma of rats following acute administration of L-dopa (50 mg kg−1, p.o. or i.a.) alone or following pretreatment with carbidopa, and unaltered hepatic dopa decarboxylase activity.