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.
Wang
Li-Hsuan
LH
Department of Medicinal Chemistry, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
Hsu
Kuang-Yang
KY
Uang
Yow-Shieng
YS
Hsu
Feng-Lin
FL
Yang
Li-Ming
LM
Lin
Shwu-Jiuan
SJ
D000818:Animals; D002109:Caffeic Acids / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D002230:Carbidopa / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D003373:Coumaric Acids / Q000097:blood / Q000493:pharmacokinetics; D007980:Levodopa / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011817:Rabbits; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics
D002109:Caffeic Acids; D003373:Coumaric Acids; D014443:Tyrosine; D007980:Levodopa; C004999:ferulic acid; D002230:Carbidopa; C040048:caffeic acid; C008404:3-methoxytyrosine