Toxicity Study of CJ-10882, a Type IV Phosphodiesterase Inhibitor: 2 Weeks Repeated Oral Administration in Beagle Dogs

Type IV phosphodiesterase inhibitor(CJ-10882)의 개에 대한 2주간 경구반복투여 독성시험

  • 한정희 (한국화학연구원 부설 안전성평가연구소) ;
  • 배주현 (한국화학연구원 부설 안전성평가연구소) ;
  • 김종춘 (한국화학연구원 부설 안전성평가연구소) ;
  • 김달현 (제일제당 종합기술원 제약연구소) ;
  • 이근호 (제일제당 종합기술원 제약연구소) ;
  • 송석범 (제일제당 종합기술원 제약연구소) ;
  • 차신우 (한국화학연구원 부설 안전성평가연구소)
  • Published : 2002.06.01

Abstract

CJ-10882, (E)-[(3-Cyclopentyloxy-4-methoxyphenyl)methylene]hydrazine-carboxamide, is a newly developed type IV phosphodiesterase isozyme (PDE IV) inhibitor. To investigate the subacute toxic effects of CJ-10882, it was administered to both male and female dogs at 0, 25, 50, 100 or 200 mg/kg/day orally for up to 2 weeks. During the test period, clinical signs, mortality, body weight, food consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross finding, organ weight, and histopathology were evacuated. Several clinical signs were observed in treated dogs at above 25 mg/kg, including salivation and vomiting. A reduction in the body weight was observed in both sexes at above 50 mg/kg. There were no treatment-related effects on mortality, ophthalmoscopy, urinalysis, hematology, sect biochemistry, necropsy findings, and histopathology in any treatment group. The results of this study demonstrate that CJ-10882, a selective Inhibitor of the type IV class of PDE, may cause effects on gastrointestinal tract and salivary glands. Therefore, these organs should be closely examined in studies with other PDE IV inhibitors.

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References

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