Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Pharmacokinetics of a New Antigastritic Agent, Eupatilin, an Active Component of StillenE®, in Rats

  • Jang, Ji-Myun (Research Laboratory, Dong-A Pharmaceutical Company Ltd) ;
  • Park, Kyung-Jin (Research Laboratory, Dong-A Pharmaceutical Company Ltd) ;
  • Kim, Dong-Goo (Research Laboratory, Dong-A Pharmaceutical Company Ltd) ;
  • Shim, Hyun-Joo (Research Laboratory, Dong-A Pharmaceutical Company Ltd) ;
  • Ahn, Byung-Ok (Research Laboratory, Dong-A Pharmaceutical Company Ltd) ;
  • Kim, Soon-Hoe (Research Laboratory, Dong-A Pharmaceutical Company Ltd) ;
  • Kim, Won-Bae (Research Laboratory, Dong-A Pharmaceutical Company Ltd)
  • Published : 2003.09.01
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Abstract

Pharmacokinetics of eupatilin (an active components of $Stillen^{\circledR}$, a new antigastritic agent) were investigated after both intravenous and oral administration at a dose of 30mg/kg to rats. After intravenous administration, the plasma concentrations of unchanged eupatilin declined rapidly with a mean terminal half-life of 0.101 h. Eupatilin was eliminated fast in rats; the total body clearance was 121 mL/min/kg. Eupatilin was mainly metabolized in rats; the percentage of intravenous dose of eupatilin excreted in 24 h urine and feces as unchanged eupatilin was only 2.5 and 0.919％, respectively. Eupatilin was mainly metabolized to form its glucuronide conjugate; after intravenous administration, 15.9 and 51.7％ of intravenous dose was excreted in 24 h urine and feces, respectively, as eupatilin plus its glucuronide. After oral administration, the absolute bioavailability was only 3.86％ based on $AUC_{0-24h}$ of eupatilin plus its glucuronide. Approximately 68.5％ of oral dose was not absorbed from the entire gastrointestinal tract. Therefore, it could be concluded that the superior effect of eupatilin in experimental animal models of gastric ulcer and inflammatory bowel disease after oral administration could be due to the local action of eupatilin. Further pharmacokinetic studies to elucidate the local action of eupatilin are required.

Keywords

References

  1. Ahn, B. 0., Ryu, B. K., Ko, J. 1., Oh, T Y., Kim, S. H., Kim, W. B., Yang, J., Lee, E. B. and Haluu, K. B. (1997). Beneficial effect of DA-9601, an extract of Artemisiae Herba, on animal models of inflammatory bowel disease. J. Appl. Pharmacol., 5, 165-173
  2. Ahn, B. 0., Oh, T. Y, Ryu, B. K, Kim, S. T-L, Kim, W. B., Kang, S. H., Chun, M. S. and Yoon, J. I-I. (1998). Protective effect of DA-9601, an Artemisiae Herba extract, on radiationinduced colitis in Wistar rats . .I' Appl. Pharmacol., 6, 37-44
  3. Ahn, B. 0., Ko, K. H., on T. Y, Cho, I-I., Kim, W. B., Lee, K. J., Cho, S. W. and I-Iahm, K B. (2001). Efficacy of use of colonoscopy in dextran sulfate sodiuminduccd ulcerative colitis of rats: Evaluation of the effects of antioxidant. Int. J. Colorectal. Dis, 16,174-181 https://doi.org/10.1007/s003840000282
  4. Chiou, W. L. (1978). .Critical evaluation of the potential error in pharmacokinetic studies using the linear trapezoidal rule method for the calculation of the area under the plasma leveltime curve. J. Pharmacokin. Biopharm.. 6. 539-546 https://doi.org/10.1007/BF01062108
  5. Chiou, W. L. (1979). New calculation method for mean apparent drug volume of distribution and application to rational dosage regimen. .I. Pharm. Sci., 68, 1067-1069 https://doi.org/10.1002/jps.2600680843
  6. Chiou, W L. (1980). New calculation method of mean total body clearance of drugs and its application to rational dosage regimens. J. Pharm. Sci.. 69, 90-91 https://doi.org/10.1002/jps.2600690125
  7. Cho, I-I., Lee, K M., Oh, T. Y, Aim, B. 0., Chung, M. H., Cho, S. w., Kim, Y. B. and I-Iahm, K. B. (in press). Suppressive effects of antioxidant, extracts of Artemisia asiatica, on dimethylnitrosamineinduced fibrosis of the liver in rats . .J. Hepatol
  8. Davies, B, Morris, T. (1993). Physiological parameters in laboratory animals and humans. Pharm. Res., 10, 1093-1095 https://doi.org/10.1023/A:1018943613122
  9. Eatman, F. B., Colburn, W. A., Boxenbaum, I-I. G., Posmanter, I-I. N.. Weinfeld, R. E., Ronfeld, R., Weissman, L., Moore, J. D., Gibaldi, M., Kaplan, S. A. (1977). Pharmacokinetics of diazepam following multiple dose oral administration to healthy human subjects. J. Pharmacokin. Biopharm., 5,481-494 https://doi.org/10.1007/BF01061729
  10. Gibaldi, M, Perrier, D. (1982). Pharmacokinetics, 2nd ed. New York, Marcel Dekker
  11. I-Iahm, K. B., Kim, 1. H., You, B. M., Kim, Y. S., Cho, S. w., Yim, H., Ahn, B. O. and Kim, W. B. (1998). Induction of apoptosis with an extract of Artemisaia asiatica attenuates the severity of ceruleininduced pancreatitis in rats. Pancreas, 17, 153-157 https://doi.org/10.1097/00006676-199808000-00007
  12. Hahm, K B., Lee, K. M., Kim, Y. B., Hong, W. S., Lee, W. H., Han, S. D., Kim, M. W, Ahn, B. 0., Oh, T. Y, Lee, M. w., Green, J. and Kim, S. J. (2002). Conditional loss of TGF-~signaling leads to increased susceptibility to gastrointestinalcarcinogenesis. Alimen. Pharmacal. Then, 16 (Suppl. 2), 115127
  13. Kang, S. H., Chun, M. S., Jin, Y M., Cho, M. S., Oh, Y. T., AIm,B. O. and Oh, T. Y. (2000). A rat model for radiationinduced proctitis. 1. Korean Med. Sci., 15, 682-689 https://doi.org/10.3346/jkms.2000.15.6.682
  14. Kim, O.J, Kang, KK., Kim, D. H., Baik, N.G., Ahn, B.O., Kim, W.B. and Yang, J. (1996). Four-week oral toxicity study of DA-9601, an antiulcer agent of Artemisia spp. Extract, in rats. 1. Appl. Pharmacol., 4, 354-363
  15. Kim, S. H., Kim, S. B., Lee, S. D., Kim, W. B., Lee, M. G., Kim, N. D., (1997). Determination of a new antiulcer agent, eupatilin, in rat plasma, bile, urine, and liver homogenate by high-performance liquid chromatography. Res. Commun. Mol. Path. Pharmacol., 97,167-172
  16. Lee, M. G., Chiou, W. L. (1983). Evaluation of potential causes for the incomplete bioavailability of furosemide: gastric first-pass metabolism. J Pharmacokinet Biopharm., 11, 623-40 https://doi.org/10.1007/BF01059061
  17. Lee, J. S., Oh, T. Y, Ahn, B. 0., Cho, H., Kim, W. B., Kim, Y. B., Surh, Y J. and Hahm, K B. (2001). Involvement of oxidative stress in experimentally induced reflux esophagitis and Barrett's esophagus: Clue for the chemoprevention of esophageal carcinoma by antioxidant. Mutation Res., 480-481, 189-200 https://doi.org/10.1016/S0027-5107(01)00199-3
  18. Mitruka, B. M. and Rawnsley, H. M. (1981). Clinical Biochemical and Hematological Reference Values in Normal Experimental Animals and Normal Humans. 2nd ed. Masson Publishing, New York, N.Y
  19. Oh, T. Y, Ryu, B. K, Park, J. B., Lee, S. D., Kim, W B., Yang, 1. and Lee, E. B. (1996). Studies on antiulcer effects of DA-9601, an Artemisia Herba extract against experimental gastric ulcers and its mechanism. J. Appl. Pharmacol., 4, 111-121
  20. Oh, T. Y., Ryu, B. K., Ko, 1. 1., Ahn, B. 0., Kim, S. H., Kim, W. B., Lee, E. B., Jin, J. H. and Hahm, K B. (1997). Protective effect of DA-9601, an extract of Artemisiae Herba, against naproxeninduced gastric damage in arthritic rats. Arch. Pharm. Res., 20, 414-419 https://doi.org/10.1007/BF02973932
  21. Oh, T. Y., AIm, B. 0., Ko, J. 1., Ryu, B. K., Kim, S. H., Kim, W. B., Yang, 1. and Lee, E. B. (1997). Studies on protective effect of DA-9601, an Anemisiae Herba extract, against alcoholinduced gastric mucosal damage and its mechanism. J. Appl. Pharmacol., 5,202-210
  22. Oh, T. Y., Lee, 1. S., Ahn, B. 0., Cho, H., Kim, W. B., Kim, Y. B., Surh, Y. 1., Cho, S. w., Lee, M. W. and Hahm, K. B. (2001a). Efficacy of combination treatment of antioxidant and acid suppression in the treatment of gastroesophageal reflux disease: Implication for the complete healing. Free Rad. Biol. Med., 30, 905-915 https://doi.org/10.1016/S0891-5849(01)00472-5
  23. Oh, T. Y., Lee, J. S., AIm, B. 0., Lee, K i., Kim, W. B., Kim, Y. B., Surh, Y. 1., Cho, S. W. and Hahm, K. B. (200Ib). Oxidative stress more than acids is implicated in pathogenesis of reflux esophagitis in rats. Gut, 49, 364-371 https://doi.org/10.1136/gut.49.3.364
  24. Ryu, B. K, Aim, B. 0" Oh, T Y, Kim, S. H., Kim, W. B. and Lee, E. B. (1998). Studies on protective effect of DA-9601, Artemisia asiatica extract, on acetaminophen and CCI4induced liver damage. Arch. Pharm. Res., 21, 508-513 https://doi.org/10.1007/BF02975366
  25. Seo, H. J. and Surh, Y. J. (2001). Eupatilin, a pharmacologically active flavone derived from Artemisia plants, induces apoptosis in human promyelocytic leukemia cells. Mutation Res., 496, 191-198 https://doi.org/10.1016/S1383-5718(01)00234-0