Caffeic acid improves the bioavailability of L-dopa in rabbit plasma

The impacts of caffeic acid (3,4-dihydroxycinnamic acid, CA) on the pharmacokinetics of levodopa (L-dopa) were studied in rabbits. A single dose of 5/1.25 mg·kg^-1 L-dopa/carbidopa was administered alone or was coadministered with three different doses of caffeic acid (2.5, 5, and 10 mg·kg^-1), or a single dose of 5 mg·kg^-1 caffeic acid was administered alone via an intramuscular route to six rabbits each in a crossover treatment protocol. Plasma levels of L-dopa, 3-O-methyldopa (3-OMD), caffeic acid, and ferulic acid were determined and subsequently used to calculate their pharmacokinetic parameters. The results indicated that caffeic acid administered at a dose of 10 mg·kg^-1 decreased about 22% of the peripheral formation of 3-OMD and about 31% of the C_max of 3-OMD. In addition, the metabolic ratios (MR, AUC of 3-OMD/AUC of L-dopa) decreased by about 22%. Results also indicated that caffeic acid significantly decreased the proportion of 3-OMD (p < 0.05). In contrast, the parameters of neither caffeic acid nor ferulic acid were significantly affected by L-dopa/carbidopa. In conclusion, caffeic acid at a dose of 10 mg·kg ^-1 can significantly affect the COMT metabolic pathway of L-dopa.