Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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Effects of Oral Rutaecarpine on the Pharmacokinetics of Intravenous Chlorzoxazone in Rats

  • Published : 2008.09.01
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Abstract

It has been reported that hepatic microsomal cytochrome P450(CYP) 2E1 is responsible for the metabolism of chlorzoxazone(CZX) to 6-hydroxychlorzoxazone. The present study was undertaken to assess the possible interaction of rutaecarpine, an alkaloid originally isolated from the unripe fruit of Evodia rutaecarpa, with CZX. Male Spraque-Dawley rats were administered with 80 mg/kg/day of oral rutaecarpine for three consecutive days. Twenty four hr after the pre-treatment with rutaecarpine, the rats were treated with 20 mg/kg of intravenous CZX. Rat hepatic microsomes isolated from rutaecarpine-treated rats showed greater(50% increase) activity of p-nitrophenol hydroxylase(a marker of CYP2E1) when compared with the control rats. Compared with control rats, the AUC of CZX was significantly smaller(84% decrease) possibly due to significantly faster CL(646% increase) in rats pretreated with rutaecarpine. This could be, at least partially, due to induction of CYP2E1 by rutaecarpine.

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References

  1. Chiou, W.F., Liao, J.P. and Chen, C.F. (1996). Comparative study of the vasodilatory effects of three quinazoline alkaloids isolated from Evodia rutaecarpa. J. Nat. Prod., 59, 374-378 https://doi.org/10.1021/np960161+
  2. Chiou, W.L. (1978). Critical evaluation of the potential error in pharmacokinetic studies of using the linear trapezoidal rule method for the calculation of the area under the plasma level - time curve. J. Pharmacokinet. Biopharm., 6, 539-546 https://doi.org/10.1007/BF01062108
  3. Conney, A.H. and Burns, J.J. (1960). Physiological disposition and metabolic fate of chlorzoxazone (paraflex) in man. J. Pharmacol. Exp. Ther., 128, 340-343
  4. Desiraju, R.K., Renzi, N.L. Jr., Nayak, R.K. and Ng, K.T. (1983). Pharmacokinetics of chlorzoxazone in humans. J. Pharm. Sci., 72, 991-994 https://doi.org/10.1002/jps.2600720905
  5. Frye, R.F. and Stiff, D.D. (1996). Determination of chlorzoxazone and 6-hydroxychlorzoxazone in human plasma and urine by high-performance liquid chromatography. J. Chromatogr. B, 86, 291-296
  6. Perrier, D. and Gibaldi, M. (1982). General derivation of the equation for time to reach a certain fraction of steady state. J. Pharm. Sci., 71, 474-475 https://doi.org/10.1002/jps.2600710432
  7. Han, E.H., Jeong, T.C. and Jeong, H.G. (2007). Effects of formononetin on the aryl hydrocarbon receptor and 7,12- dimethylbenz[a]anthracene-induced cytochrome P450 1A1 in MCF-7 human breast carcinoma cells. J. Toxicol. Pub. Health, 23, 135-142 https://doi.org/10.5487/TR.2007.23.2.135
  8. Jan, W.C., Lin, L.C., Chen, C.F. and Tsai, T.H. (2005). Herbdrug interaction of Evodia rutaecarpa extract on the pharmacokinetics of theophylline in rats. J. Ethnopharmacol., 102, 440-445 https://doi.org/10.1016/j.jep.2005.07.002
  9. Kim, D. and Chun, Y.J. (2007). Human cytochrome P450 metabolic activation in chemical toxicity. J. Toxicol. Pub. Health, 23, 189-196 https://doi.org/10.5487/TR.2007.23.3.189
  10. Koop, D.R. (1986). Hydroxylation of p-nitrophenol by rabbit ethanol-inducible cytochrome P450 isozyme 3a. Mol. Pharmacol., 29, 399-404
  11. Lee, S.H., Kim, S.I., Park, J.G., Lee, E.S. and Jahng, Y. (2001). A simple synthesis of rutaecarpine. Heterocycles, 55, 1555-1559 https://doi.org/10.3987/COM-01-9244
  12. Lee, S.K., Bista, S.R., Jeong, H., Kim, D.H., Kang, M.J., Jahng, Y. and Jeong, T.C. (2007). The effects of rutaecarpine on the pharmacokinetics of acetaminophen in rats. Arch. Pharm. Res., 30, 1629-1634 https://doi.org/10.1007/BF02977334
  13. Lee, S.K., Kim, N.H., Lee, J., Kim, D.H., Lee, E.S., Choi, H.G., Chang, H.W., Jahng, Y. and Jeong, T.C. (2004a). Induction of cytochrome P450s by rutaecarpine and metabolism of rutaecarpine by cytochrome P450s. Planta Med., 70, 753-757 https://doi.org/10.1055/s-2004-827207
  14. Lee, S.K., Lee, D.W., Jeon, T.W., Jin, C.H., Kim, G.H., Jun, I.H., Lee, D.J., Kim, S.I., Kim, D.H., Jahng, Y. and Jeong, T.C. (2005). Characterization of the phase 2 metabolites of rutaecarpine in rats by liquid chromatography-electrospray ionization-tandem mass spectrometry. Xenobiotica, 35, 1135-1145 https://doi.org/10.1080/00498250500363742
  15. Lee, S.K., Lee, J., Lee, E.S., Jahng, Y., Kim, D.H. and Jeong, T.C. (2004b). Characterization of in vitro metabolites of rutaecarpine in rat liver microsomes using liquid chromatography/ tandem mass spectrometry. Rapid Commun. Mass Spectrom., 18, 1073-1080 https://doi.org/10.1002/rcm.1448
  16. Lee, S.K., Yoo, H.H., Kim, D.H., Jahng, Y. and Jeong, T.C. (2006). Characterization of human liver cytochrome P450 enzymes involved in the metabolism of rutaecarpine. J. Pharmaceut. Biomed. Anal., 41, 304-309 https://doi.org/10.1016/j.jpba.2005.10.039
  17. Lowry, O.H., Rosenbrough, N.J., Farr, A.L. and Randall, R.J. (1951). Protein measurement with the folin phenol reagent. J. Biol. Chem., 193, 265-275
  18. Moon, T.C., Murakami, M., Kudo, I., Son, K.H., Kang, S.S. and Chang, H.W. (1999). A new class of COX-2 inhibitor, rutaecarpine from Evodia rutaecarpa. Inflamm. Res., 48, 621-625 https://doi.org/10.1007/s000110050512
  19. Peter, R., Böcker, R., Beaune, P.H., Iwasaki, M., Guengerich, F.P. and Yang, C.S. (1990). Hydroxylation of chlorzoxazone as a specific probe for human liver cytochrome P- 450IIE1. Chem. Res. Toxicol., 3, 566-573 https://doi.org/10.1021/tx00018a012
  20. Rockich, K. and Blouin, R. (1999). Effect of the acute-phase response on the pharmacokinetics of chlorzoxazone and cytochrome P-450 2E1 in vitro activity in rats. Drug Metab. Dispos., 27,1074-1077
  21. Tsai, T.H., Chang, C.H. and Lin, L.C. (2005). Effects of Evodia rutaecarpa and rutaecarpine on the pharmacokinetics of caffeine in rats. Planta Med., 71, 640-645 https://doi.org/10.1055/s-2005-871270
  22. Ueng, Y.F., Ko, H.C., Chen, C.F., Wang, J.J. and Chen, K.T. (2002). Modulation of drug-metabolizing enzymes by extracts of a herbal medicine Evodia rutaecarpa in C57BL/ 6J mice. Life Sci., 71, 1267-1277 https://doi.org/10.1016/S0024-3205(02)01854-4
  23. Ueng, Y.F., Tasi, T.H., Don, M.J., Chen, R.M. and Chen, T.L. (2005). Alteration of the pharmacokinetics of theophylline by rutaecarpine, an alkaloid of the medicinal herb Evodia rutaecarpa, in rats. J. Pharm. Pharmacol., 57, 227-232 https://doi.org/10.1211/0022357055489
  24. Woo, H.G., Lee, C.H., Noh, M.S., Lee, J.J., Jung, Y.S., Baik, E.J., Moon, C.H. and Lee, S.H. (2001). Rutaecarpine, a quinazolinocarboline alkaloid, inhibits prostaglandin production in RAW264.7 macrophages. Planta Med., 67, 505-509 https://doi.org/10.1055/s-2001-16479
  25. Yang, K.H. and Lee, M.G. (2007). Effects of lipopolysaccharide on pharmacokinetics of drugs. J. Toxicol. Pub. Health, 23, 289-299 https://doi.org/10.5487/TR.2007.23.4.289