Effects of Evodia rutaecarpa and Rutaecarpine on the Pharmacokinetics of Caffeine in Rats

Abstract

To assess possible herb-drug interactions, rutaecarpine (an herbal ingredient of Evodia rutaecarpa; 25 mg/kg/day, p. o.), the ethanol extract of Evodia rutaecarpa (1 g/kg/day, p. o.), and an herbal preparation of Evodia rutaecarpa (Wu-Chu-Yu-Tang; 1 g/kg/day) were individually pretreated daily for three consecutive days in rats and on the fourth day caffeine was administered (2 mg/kg, i. v.). Caffeine concentrations in blood, brain and bile were concurrently measured by microdialysis coupled to a liquid chromatographic system. Pharmacokinetic data were calculated by a non-compartmental model. The results indicate that the caffeine crosses the blood-brain barrier and goes through hepatobiliary excretion. The caffeine level was significantly decreased by the pretreatment of rutaecarpine, the extract of Evodia rutaecarpa and herbal preparation Wu-Chu-Yu-Tang. This finding should be very important whenever herb-drug interactions would be possible for a herbal remedy.

Caffeine - Evodia rutaecarpa - Rutaceae - microdialysis - pharmacokinetics - rutaecarpine - traditional Chinese medicine

References

• 1 Chen L, Bondoc F Y, Lee M J, Hussin A H, Thomas P E, Yang C S. Caffeine induces cytochrome P4501A2: induction of CYP1A2 by tea in rats.  Drug Metab Dispos. 1996;  24 529-33
• 2 Asahina Y, Kashiwaki K. 1915. Chemical constituents of the fruits of Evodia rutaecarpa .  J Pharm Soc Jpn. 1915;  35 293
• 3 Ueng Y F, Wang J J, Lin L C, Park S S, Chen C F. Induction of cytochrome P450-dependent monooxygenase in mouse liver and kidney by rutaecarpine, an alkaloid of the herbal drug Evodia rutaecarpa .  Life Sci. 2001;  70 207-17
• 4 Tang W, Eisenbrand G. Evodia rutaecarpa (Juss) Benth, in Chinese Drugs of Plant Origin. Tang W, Eisenbrand, G, eds Springer-Verlag Berlin; 1992: pp 509-14
• 5 Kano Y, Zong Q, Komatsu K. 1991. Pharmacological properties of galenical preparation, XIV. Body temperature retaining effect of the Chinese traditional medicine, ”Goshuyu-to” and component crude drugs.  Chem Pharm Bull. 1991;  39 690-2
• 6 Tsai T H. Assaying protein unbound drugs using microdialysis techniques.  J Chromatogr B. 2003;  797 161-73
• 7 Tsai T H, Chen Y F, Chen I F, Chen C F. Measurement of unbound caffeic acid in rat blood by on-line microdialysis coupled with liquid chromatography and its application to pharmacokinetic studies.  J Chromatogr B. 1999;  729 119-25
• 8 Tsai T H. Pharmacokinetics of pefloxacin and its interaction with cyclosporin A, a P-glycoprotein modulator, in rat blood, brain and bile, using simultaneous microdialysis.  Brit J Pharmacol. 2001;  132 1310-6
• 9 Scott D O, Lunte C E. In vivo microdialysis sampling in the bile, blood, and liver of rats to study the disposition of phenol.  Pharm Res. 1993;  10 335-42
• 10 Paxinos S, Watson C. The Rat Brain in Stereotaxic Coordinates. 1982 Academic Press Sydney;
• 11 Tsai T H, Lee C H, Yeh P H. Effect of cyclosporine, a P-glycoprotein modulator, on the disposition and biliary excretion of camptothecin using microdialysis.  Brit J Pharmacol. 2001;  134 1245-52
• 12 Tsai T H, Liu S C, Tsai P L, Ho L K, Shum A YC, Chen C F. Pharmacokinetics of baicalein and its interaction with P-glycoprotein inhibitor, cyclosporin A, in the rat: a microdialysis study.  Brit J Pharmacol. 2002;  137 1314-20
• 13 Tsai P L, Tsai T H. Hepatobiliary excretion of berberine.  Drug Metab Dispos. 2004;  32 405-12
• 14 McCall A L, Millington W R, Wurtman R J. Blood-brain barrier transport of caffeine: dose-related restriction of adenine transport.  Life Sci. 1982;  31 709-15
• 15 Holstege A, Kurz M, Weinbeck M, Gerok W. Excretion of caffeine and its primary degradation products into bile.  J Hepatol. 1993;  17 67-73
• 16 Beach C A, Mays D C, Sterman B M, Gerber N. Metabolism, distribution, seminal excretion and pharmacokinetics of caffeine in the rabbit.  J Pharmacol Exp Ther. 1985;  233 18-23
• 17 Lin J H, Sugiyama Y, Awazu S, Hanano M. (1982) In vitro and in vivo evaluation of the tissue-to-blood partition coefficient for physiological pharmacokinetic models.  J Pharmacokinet Biopharm. 1982;  10 637-47
• 18 Ueng Y F, Jan W C, Chen T L, Guengerich F P, Chen C F. The alkaloid rutaecarpine is a selective inhibitor of cytochrome P450 1A in mouse and human liver microsomes.  Drug Metab Dispos. 2002;  30 349-53
• 19 Ayalogu E O, Snelling J, Lewis D FV, Talwar S, Clifford M N, Ioannides C. (1995) Induction of hepatic CYP1A2 by the oral administration of caffeine to rats: lack of association with the Ah locus.  Biochim Biophys Acta. 1995;  1272 89-94
• 20 Berthou F, Goasduff T, Dreano Y, Menez J F. Caffeine increases its own metabolism through cytochrome P4501A induction in rats.  Life Sci. 1995;  57 541-9
• 21 Roberts E A, Furuya K N, Tang B K, Kalow W. Caffeine biotransformation in human hepatocyte lines derived from normal liver tissue.  Biochem Biophy Res Commun. 1994;  201 559-66
• 22 Ha H R, Chen J, Krahenbuhl S, Follath F. Biotransformation of caffeine by cDNA-expressed human cytochromes P-450.  Eur J Clin Pharmacol. 1996;  49 309-15
• 23 Ursing C, Wikner J, Brismar K, Rojdmark S. Caffeine raises the serum melatonin level in healthy subjects: an indication of melatonin metabolism by cytochrome P450(CYP)1A2.  J Endocrinol Inv. 2003;  26 03-6