Circadian phase dependent pharmacokinetics of L-dopa, its main metabolites (3-OMD, HVA, DOPAC) and carbidopa in rats

Abstract

This study aims to evaluate whether or not the kinetics of L-dopa, its main metabolites (3-O-methyldopa, 3-OMD, homovanilic acid, HVA and 3,4-dihydroxyphenylacetic acid, DOPAC) and carbidopa, vary according to the 24-hour scale in rats. Four groups of seven adult male Wistar AF EOPS rats were used for these experiments; each group received L-dopa (200 mg.kg-1 ip) and carbidopa (20 mg.kg-1 ip) at 1000, 1600, 2200 or 0400 hours. L-dopa, 3-OMD, DOPAC, HVA and carbidopa were simultaneously determined by specific ion-pair reversed-phase high performance liquid chromatography with electrochemical detection. A temporal variation of the kinetics of both L-dopa and carbidopa was demonstrated with higher plasma clearance and lower area under concentration curve after the administration at 2200 hours. Moreover, a temporal variation of the metabolism of L-dopa was indirectly documented by temporal variation in kinetics of 3-OMD, DOPAC and HVA.