Abstract:
Objective: The present study was aimed to explore the 28 days sub-acute oral toxicity
study of Roflumilast in Swiss Albino mice. Information related to possible health
hazards, estimate of No-Observed-Adverse-Effect-Level (NOAEL), hematology,
biochemistry, organ weight & histopathological parameters were studied.
Experimental work: Swiss albino mice of both sexes (5-9 weeks) were divided into
four groups, each consisting of six male and six female mice. Group I (Corn oil),
Group II (0.25 mg/kg), III (2.5 mg/kg) and IV (25 mg/kg) were dosed at 10mL/kg
body weight, daily once orally for 28 days.Clinical signs (daily); body weight & feed
consumption (weekly) were taken. Blood samples were collected by retro-orbital
plexus before necropsy (29th day). Target organs were stored in 10% formal saline.
Statistical analysis was performed using One way ANOVA followed by Duncan's
New Multiple Range Test (DNMRT).
Results and Discussion: No mortality or adverse clinical signs change in body
weight, feed consumption was observed as compared to control. Hematological and
Biochemical variations were observed in some parameters. In target organs no
significant changes were observed. Histopathological findings observed in Liver, Lung, Uterus, Kidney, Thymus ,Intestine and Adrenal. Here all lesions founded in
control and in treated group. so lesions are not related to Roflumilast toxicity.
Conclusion:Roflumilast is safer drug of class of PDE 4 inhibitors.Nephrotoxicity,
hepatotoxicity and thyrotoxicity not seen from results. NOAEL of Roflumilast was at
the level of 25 mg/kg for mice.