28-day oral toxicity study with soft corticosteroid BNP-166 in rats and dogs, followed by a 14-day recovery period.
The aim of the present study was to evaluate the soft corticosteroid BNP-166 in rats and dogs treated orally with 0.2, 2.0, and 20.0 mg/kg for 28 days and the reversibility of any abnormalities during a 14-day post-dosing period. The test substance, BNP-166, was well tolerated during the 28-day treatment period. The observed changes were all characteristic for the pharmacological actions of a glucocorticoid. Treatment related changes occurred in the adrenals and thymus, and, to a lesser extent, in the lymph nodes, spleen and liver. There were no statistically significant reductions in the cortisol levels of all groups in the 0.2 and 2 mg/kg treatments. Significant reductions were observed in the high-dose group (20 mg/kg), but levels returned to normal by the end of the 14-day recovery period. Based on the results, the No Observable Adverse Effect Level (NOAEL) of BNP-166 soft corticosteroid in rat and dog after 28-day oral administration is 2 mg/kg. This value is approximately 40 times higher than that of budesonide. Pharmacodynamic and receptor binding studies have shown BNP-166 to have a similar potency to budesonide; therefore, BNP-166 can be considered safer when administered orally than other corticosteroids such as prednisolone or budesonide.
Miklós
A
A
IVAX Institute for Drug Research, Budapest, Hungary. Andras_Miklos@ivax.com
Magyar
Z
Z
Kiss
E
E
Novák
I
I
Grósz
M
M
Nyitray
M
M
Dereszlay
I
I
Czégeni
E
E
Druga
A
A
Howes
J
J
Bodor
N
N
D000305:Adrenal Cortex Hormones / Q000633:toxicity*; D000311:Adrenal Glands / Q000473:pathology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004285:Dogs; D005260:Female; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D051381:Rats; D013045:Species Specificity; D013950:Thymus Gland / Q000473:pathology
D000305:Adrenal Cortex Hormones; C450000:etiprednol dicloacetate