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Four-week repeated dose oral toxicity study of KDS2010, a novel selective monoamine oxidase B inhibitor, in Sprague Dawley rats
- Source :
- Regulatory Toxicology and Pharmacology. 117:104733
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
Abstract
- Repeated dose oral toxicity and toxicokinetic of KDS2010, a new drug for Parkinson's disease, was investigated after 4-week repeated oral administration at 30, 50, 75, or 100 mg/kg/day in rats. Body weight and body weight gain decreased in rats of both sexes in the 75 and 100 mg/kg groups, and food consumption was reduced in male rats of the 75 and 100 mg/kg male groups. Histological alterations were observed in the kidney (urothelial hyperplasia, inflammatory cell infiltration in the renal pelvis, tubular vacuolation/degeneration, basophilic tubules, and hyaline droplets in the proximal tubules) of the 75 and 100 mg/kg male groups and the 50 and 100 mg/kg female groups. The 75 and 100 mg/kg male groups showed adverse effect in the testes (degeneration/exfoliation of germ cells, seminiferous tubules atrophy) and epididymis (cellular debris, oligospermia). These changes were partially recovered after a 2-week recovery period. However, basophilic tubules and hyaline droplets in the proximal tubules in the kidney and germ cell degeneration/exfoliation in the testis were not recovered. In toxicokinetics study, systemic exposure to KDS2010 increased proportionally in both sexes by in a dose -dependent manner. In addition, repeated administration for 4 weeks led to increased tendency of systemic exposure in both sexes compared with that in Day 1. In conclusion, KDS2010 was shown to target the kidney and testis with a no-observed-adverse-effect level of 50 and 30 mg/kg/day for males and females, respectively.
- Subjects :
- Male
medicine.medical_specialty
Monoamine Oxidase Inhibitors
Time Factors
No-observed-adverse-effect level
Administration, Oral
010501 environmental sciences
Toxicology
030226 pharmacology & pharmacy
01 natural sciences
Rats, Sprague-Dawley
03 medical and health sciences
0302 clinical medicine
Atrophy
Oral administration
Internal medicine
medicine
Animals
Toxicokinetics
Toxicity Tests, Chronic
Monoamine Oxidase
Hyaline
0105 earth and related environmental sciences
Kidney
Dose-Response Relationship, Drug
business.industry
General Medicine
medicine.disease
Epididymis
Rats
Basophilic
medicine.anatomical_structure
Endocrinology
Female
business
Subjects
Details
- ISSN :
- 02732300
- Volume :
- 117
- Database :
- OpenAIRE
- Journal :
- Regulatory Toxicology and Pharmacology
- Accession number :
- edsair.doi.dedup.....891fc187c99816b693e1e8b80537c870