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 co‐administered 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. Copyright © 2009 John Wiley & Sons, Ltd.