A 90-day Repeat-Dose Oral Toxicity Study of Yonkenafil Hydrochloride in Beagle Dogs

Yonkenafil hydrochloride, a novel synthetic phosphodiesterase type 5 inhibitor, is a promising drug for the treatment of erectile dysfunction. The repeated-dose toxicity of yonkenafil hydrochloride was assessed in male and female beagle dogs. Twenty-four dogs were randomly allocated to four groups and administered yonkenafil hydrochloride orally at dosages of 0, 7, 30 or 120 mg/kg/day for 90 days followed by a 28-day recovery period. During the test period, clinical signs, mortality, body weight, food consumption, ophthalmoscopy, electrocardiography, hematology, serum biochemistry, urinalysis, organ weights, gross findings and histopathology were examined. There were no abnormal changes in the clinical observations except that gastrointestinal intolerance was observed in the 120 mg/kg/day group. The laboratory and histopathological examinations revealed yonkenafil hydrochloride toxicity to various organs, including the thyroid gland, liver, prostate, uterus and breast; at the end of the recovery period, this damage was resolved. The level of yonkenafil hydrochloride that resulted in no observable adverse effects in beagle dogs was 7 mg/kg/day.