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 Cmax 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.

Li-Hsuan Wang 1, Kuang-Yang Hsu 2, Yow-Shieng Uang 3, Feng-Lin Hsu 4, Li-Ming Yang 1 5, Shwu-Jiuan Lin 1 *
1Department of Medicinal Chemistry, College of Pharmacy, Taipei Medical University, 250 Wu-Hsing St., Taipei 110, Taiwan
2Department of Pharmaceutics, College of Pharmacy, Taipei Medical University, 250 Wu-Hsing St., Taipei 110, Taiwan
3Rosetta Pharmamate Co., Ltd, 3rd Fl., No. 2, Lane 130, Min-Chiuan Rd., Shindian City, Taipei 231, Taiwan
4Graduate Institute of Pharmacognosy, College of Pharmacy, Taipei Medical University, 250 Wu-Hsing St., Taipei 110, Taiwan
5Division of Medicinal Chemistry, National Research Institute of Chinese Medicine 155-1 Li-Nong St., Sec. 2, Taipei 112, Taiwan
 
email: Shwu-Jiuan Lin ( This e-mail address is being protected from spambots. You need JavaScript enabled to view it. )

*Correspondence to Shwu-Jiuan Lin, Department of Medicinal Chemistry, College of Pharmacy, Taipei Medical University, 250 Wu-Hsing St., Taipei 110, Taiwan

Funded by:
 National Science Council of Taiwan; Grant Number: NSC96-2320-B-038-013