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¡¡ÒÔÏÂÀ¶É«×ÖÌåµÄÊÇÐèÒª·ÒëµÄ£¬¹²2¾ä»°£¬Ð»Ð»£¡¡¡ ¡¡£¨1£©¡¡Report 127/2002 used a finer dose selection to further investigate effects of roflumilast on preand post-natal development. Female mice (30/dose, NMRI) were given orally 0, 1.5, 3 or 6-mg/kg/day roflumilast during gestation days 6 ¨C 15 and the lactation period. Pregnancy outcomes were examined at delivery. Behavioral developmental effects were evaluated in pups. Doserelated effects on number of stillborns, litter sizes, pup viability and locomotor activity were observed in the MD and HD groups. The decreases in pup viability were observed both pre and after lactation day 4 (culling).The frequency of litters with live pups at birth, but no pups, on day 4 was 0%, 0%, 0% and 8% in C, LD, MD and HD groups,respectively.The frequency of pup deaths in the post-culling period was 1.1%, 0.3%, 3.2% and 4.5% (p < 0.05) in C, LD, MD and HD groups, respectively. The HD dams showed minimal and statistically non-significant decreases in mean body weight (3.9%). ¡¡¡¡£¨2£©Dose-related decreases in body weight were observed in all treatment groups. Significant, dose-related decreases in prostate weight were noted (down 23.6%, 27.8% and 33.3% compared to control), and HD males showed significant increases in adrenal gland weight. Histopathological findings were noted in the nasal cavity of HD females and in the adrenal cortex in HD males and females. No treatment-related effects on male fertility were observed. Systemic exposure to roflumilast and roflumilast N-oxide increased supra-proportionally to the dose. [ Last edited by xiaolu0424 on 2011-8-24 at 14:58 ] |
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