SUMMARY OF THE STUDY
The purpose of this study was to evaluate the maximum tolerated dose of LAS01 in Sprague dawley female rat. The study was performed as per regulatory guideline for selection of dose level for new pharmaceutical products. Animals were acclimatized in standard animal house environmental conditions for 5 days before the start of experiment. On last day of acclimatization, all animals were randomized on the basis of their body weight. For this study, total 10 female SD rat with age 8-12 weeks (weight 185 -200 g) were selected and divided into five groups Group1, Gr.3 , Gr.4 and Gr.5 have two animals each and orally treated with single dose of LAS01 at dose levels 1000, 2000, 3000 and 4000 mg/kg body weight respectively, where as Gr.2 has two animals and treated with normal saline (0.9%) at the dose level 10ml /kg body weight. The animals of each group monitored per day and recorded body weight, food consumption, clinical sign of toxicity and mortality for 14 days. Our finding showed that there were insignificant changes observed in body weight and food consumption of 1000, 2000, 3000mg/kg body weight of LAS01 treated group as compared to control group (Gr.2) animals. No mortality and clinical sign of toxicity were observed at dose levels of 1000 and 2000mg/ kg bodyweight in animals. A the dose level of 3000, 4000mg/kg body weight, the animals showed clear clinical sign of toxicity (loss of haring, slow movement, chemosis etc.) after 15 and 30 minute post dosing of LAS01. After one hour, at dose level of 3000 mg/kg body weight, the did not showed any abnormality regarding clinical sign of toxicity upto 14 days. At dose 4000 mg/kg body weight ,the animals appear clinical sign of toxicity for 15 and 30 minutes after animals were died. At high dose level, the animals showed gross changes in the heart organ after gross necropsy examination . On the basis of above finding it concluded that the MTD of LAS01 is 3000mg/kgbody weight in SD female rats.
The objective of this study was to evaluate the maximum tolerated dose of LAS01 in Sprague dawley female rat.
Personal protection equipments like gloves, masks, aprons, footwear were employed as required while handling the test item and test system.
MATERIALS AND METHODS
Description of the Test Procedure
Ten Sprague dawley rats (10 female) weighting 185-200g was used for the study. All animals to be acclimatized in Standard animal house environment for at least 5 days before initiation of experiment. After the acclimatization, animals to be randomized into five groups of 02 animals each . Group 2 (2male ) to be treated with base test item and serve as vehicle control group whereas Group 1,3,4 and 5 were treated with test item LAS01 at dose levels 1000, 2000,3000 and 4000 mg/Kg body weight. All animals were located into groups as given below.
|Groups||No of animal/Sex||Doses (mg/kg body weight)|
|II||2 F||Vehicle control (.9% Normal saline )|
|Vehicle control group treated with (.9% normal saline solution at 10 ml/kg body weight dose)|
Each group of animals were administrated dose single (increasing order after 24 hour observation) and observed clinical sign of toxicity and mortality and body weight and food consumption record measurement for 14 days.
Preparation of Test items
Calculated amount of test item LAS01 was used according to individual body weight of animal administered via oral route. The test item was administered to animal at 10ml /Kg body weight
Justification for selection of route of administration
Oral route is the intended route for test item as suggested by the sponsor on the basis of intended use of formulation.
All group of each animals were recorded body weight per day for 14 day
Each cage of animals were offered 200 gm per day pelleted feed and consumption was recorded next day for 14 days. Feed intake by animals were calculated by deducting the amount of feed consumed from the feed offered. The feed consumption was recorded throughout the experiment for 14 days.
Clinical signs of toxicity
Clinical signs of toxicity were observed in individual animal of treated groups per day for 14 days. All clinical signs of toxicity were recorded per day in raw data sheet for 14 days .
All animals were observed twice daily for morbidity/mortality during the entire experimental period.
Necropsy was performed for animals in severe distress / morbid condition and on study termination to observe any test item related toxicity.
On the basis of above parameters, it is concluded that the test item LAS01 showed maximum tolerated dose (MTD) 3000 mg/kg body weight as evidence on the basis of body weight, feed consumption and clinical sign of toxicity parameters in SD female rats.
There was insignificant Change observed in the body weight of all dose of treated groups (Gr.1,3,4 and 5) as compared to control group (Gr.2). The body weight was gradually increased on 7th and 14th day as compared with control group. (See Chart: BW & BW%)
There was insignificant Change observed in the food consumption of all dose of treated groups (Gr.1,3,4 and 5) as compared to control group (Gr.2). The feed consumption was gradually increased on 7th and 14th day as compared with control group. (See Chart: FI & FI%)