Korean Journal of Veterinary Research (대한수의학회지)

The Korean Society of Veterinary Science (대한수의학회)
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Hepatotoxicity in treatment of canine dermatophytosis with ketoconazole

피부사상균 감염개에서 Ketoconazole 경구투여시의 간독성에 관한 연구

  • Bae, Seong-su (College of Veterinary Medicine, The Institute of Animal Medicine, Gyeongsang National University) ;
  • Kim, Cheol-ho (Gyeongsangnam-do Livestock Promotion Institute) ;
  • Kim, Tae-yung (Animal Health Division, Ministry of Agriculture and Forestry) ;
  • Kang, Chung-boo (College of Veterinary Medicine, The Institute of Animal Medicine, Gyeongsang National University)
  • 배성수 (경상대학교 수의과대학 동물의학연구소) ;
  • 김철호 (경상남도 축산진흥연구소) ;
  • 김태융 (농림부 가축방역과) ;
  • 강정부 (경상대학교 수의과대학 동물의학연구소)
  • Accepted : 2005.05.27
  • Published : 2005.06.30
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Abstract

The purpose of this study is to compare hepatotoxicity of each treatment for dermatophytosis; one is the administration of the ketoconazole only and the other, ketoconazole with diphenyl-dimeththyl-dicarboxylate. Have chosen the range of 14-24 months of healthy dogs divided by two groups (group 1 and group 2) for the experiment of which test proved positive in dermatophytosis diagnosis and showed normal reaction in terms of physical examination, blood chemistry and especially of liver function. Group 1 was administrated ketoconazole orally at 10 mg/kg/day and of same dose of ketoconazole with diphenyl-dimethyl-dicarboxylate for group 2. After administering, we have tested two groups by blood collecting every one week in order to check the differences of hepatotoxicity state through AST, ALT and r-GTP, the barometers of liver function which lasted for 12 weeks. Moreover, tested Indocyanine Green (ICG), known as susceptible gauge of function of excretion before starting the experiment and tested ICG as well after 12 weeks. The experiment of result the value of group 1 in AST, ALT and r-GTP has been highly rised after administering ketoconazole for 10 weeks meanwhile, of group 2 has shown a steady state troughout the whole experiment. For ICG test, we injected 0.5 mg/kg of ICG into a vein for both groups and tested the retention rate at regular interval of 15, 30, 45 minutes. The results of retention rate in two groups were similar to before the drug administration. However, after 12 weeks the retention rate of group 1 has been delayed, on the other hand, retention rate of group 2 were a steady state. In conclusion, the administration of ketoconazole only for a long period of time induced hepatotoxicity where as, the administration of ketoconazole with diphenyl-dimethyl-dicarboxylate didn't induce hepatotoxicity. Therefore, when doctors prescribes for a dog with dermatophytosis should not administrate ketoconnazole itself but with diphenyl-dimethyl-dicarboxylate and one who has abnormal condition of liver function should not be prescribed ketoconazole treatment. If there is a case needed to prescribe ketoconazole treatment, the regular monitoring should be accompanied by at the same time.

Keywords

References

  1. 김철호, 최일관, 손민수, 김진구, 강정부. 개에서의 indocyanine green 배설시험 및 혈장효소 활성치의 변화. 대한수의학회지 1992, 32, 671-675
  2. 김형식, 이수택, 김대곤, 안득수. 안형식. 만성 간질환에 대한 Dipheny-dimethyl-dicarboxlate의 안전성 및 효과. 대한간학회지 1996, 2, 54-60
  3. 이성엽, 이창우. 한국흑염소에 있어서 Indocyanine Green 배설시험. 한국임상수의학회지 1987, 4, 29-37
  4. 이헌주, 최준혁, 최형철, 하정희. Thioacetamide 유발 급성 간 손상에 대한 Diphenyl dimethyl dicarboxylate의 효과. 대한내과학회지 1998, 54, 804-903
  5. 장화석, 문영찬, 이상원, 김휘율, 김태종. 개에서 분리한 진균의 동정과 PCR을 이용한 진단. 한국임상수의학회지 2004, 21, 35-44
  6. 주진숙. 실험쥐의 피부사상균증 및 분리균의 항진균제에 대한 감수성. 경북대학교 석사논문. 1998
  7. 최원필, 윤성웅, 송동준, 이춘식, 김영은, 박철정. Microsporum canis에 의한 개의 피부사상균증 및 개, 고양이의 피부사상균의 보균현황. 대한수의학회지 1993, 33, 235-239
  8. Birchard SJ, Sherding RG. Saunders Manual of Small Animal Pratice. 2nd Edition. pp. 141-145, 317-323, Saunders Philadelphia, 1999
  9. Brusko CS, Marten JT. Ketoconazole hepatotoxicity in a patient treated for environmental illness and systemic candidiasis. DICP, Ann Pharmacother 1991, 25, 1321-1325
  10. Chien RN, Yang LJ, Lin PY, Liaw YF. Hepatic injury during ketoconazole therapy in patients with onychomycosis: A controlled cohort study. Hepatology 1997, 25, 103-107 https://doi.org/10.1002/hep.510250119
  11. Donna WA, Danny W. Use of ketoconazole in treatment of dermatophytosis in a dog. J Am Vet Med Assoc 1987, 190, 1433-1434
  12. Findor JA, Sorda JA, Igartua ER, Avaginina A. Ketoconazole induced liver damage. Medicina (B Aires) 1998, 58, 277-281
  13. Karen AM. Treatment of dermatophytosis in dogs and cats: Review of published studies. Vet Derma 2004, 15, 99-107 https://doi.org/10.1111/j.1365-3164.2004.00361.x
  14. Kenneth AA, Koseph T, Giselle H. Blastomycosis in dogs: 115 cases(1980-1995). J Am Vet Med Assoc 1998, 213, 658-663
  15. Ketter SG, Wiegand BD, Rapaport E. Hepatic uptake and Biliary excretion of indocyanine green and its use in estimation of hepatic blood flow in dogs. Am J Physiol 1960, 199, 481-489
  16. Kuroha M, Kayaba H, Kishimoto S, Khalil WF, Shimoda M, Kokue E. Effect of oral Ketoconazole on first-pass effect of nifedipine after oral administration in dogs. J Pharm Sci 2002, 91, 868-873 https://doi.org/10.1002/jps.10086
  17. Kuroha M, Shiral Y, Shimoda M. Multiple oral dosing of ketoconazole influences phatmacokinetics of quinidine after intravenous and oral administration in beagle dogs. J Vet Pharmacol Therap 2004, 27, 355-359 https://doi.org/10.1111/j.1365-2885.2004.00610.x
  18. Kuroha M, Yoji K, Minoru S, Eiichi K. In vitro characterization of the inhibitory effects of ketoconazole on metabolic activities of cytochrome P-450 in canine hepatic microsomes. Am J Vet Res 2002, 63, 900-905 https://doi.org/10.2460/ajvr.2002.63.900
  19. Lake-Bakaar G, Scheuer PJ, Sherlock S. Hepatic reaction associated with ketoconazole in the United Kingdom. Br Med J 1987, 294, 419-422 https://doi.org/10.1136/bmj.294.6569.419
  20. Lewis JH, Zimmerman HJ, Bendon GD, Ishak KG. Hepatic injury associated with ketoconazole therapy. Analysis of 33 cases. Gastroenterology 1984, 86, 503-513
  21. Maertens JA. History of the development of azole derivatives. Clin Microbiol Infect 2004, 10, 1-10
  22. Ma YM, Ma ZQ, YAO JS, SUN RY. Hepatotoxicity and toxicokinetics of ketoconazole in rabbits. Acta Pharmacol Sin 2003, 24, 778-782
  23. Megnin P. Nouvelle maladie parasitaire de la peau chez un coq. Compt Rend Soc Biol 1881, 33, 404
  24. Miller WH, Scott DW, Griffin CE. Small animal dermatology. 5th ed. pp. 316-372, Saunders Philladelphia, 1995
  25. Rosario C. Generalized Microsporum canis dermatophytos is in six Yorkshire terrier dogs. Vet Derma 2004, 15, 181-187 https://doi.org/10.1111/j.1365-3164.2004.00368.x
  26. Rodriguez RJ, Acosta D. Jr. N-Deacetyl ketoconazole induced hepatotoxicity in a primary culture system of rat hepatocytes. Toxicology 1996, 117, 123-131 https://doi.org/10.1016/S0300-483X(96)03560-3
  27. Rodriguez RJ, Proteau PJ, Marquez BL, Hetherington CL, Buckholz CJ, O'Connell KL. Flivin containing monooxygenase mediated metabolism of N-Deacetyl ketoconazole by rat hepatic microsomes. Am Soc Pharma & Experi Thera 1999, 27, 880-886
  28. Stricker BH, Blok AP, Bronkhorst FB, Van Parys GE, Desmet VJ. Ketoconazole-Associated hepatic injury a clinicopathological study of 55 cases. J Hepato 1986, 3, 399-406 https://doi.org/10.1016/S0168-8278(86)80495-0
  29. Weiss R, Weber A. Cultural demonstration of dermatophytosis in pets with skin lesions. Praktische Tierurzl 1983, 64, 827-830
  30. Wheeler HO, Cranston WI, Meltzer JI. Hepatic uptake and biliary excretion of indocyanine green in the dog. Proc Soc Exp Biol Med 1958, 99, 11-19