VALIDATED HPTLC METHOD OF ANALYSIS OF NIMESULIDE IN BLOOD AND TISSUE DISTRIBUTION IN DIFFERENT ORGANS OF RATS
Journal Title: International Research Journal of Pharmacy (IRJP) - Year 2012, Vol 3, Issue 10
Abstract
Nimesulide, (4-nitro-2-phenoxymethane-sulfoanilide), a NSAID compound has been used in human and veterinary medicine having a selective cyclooxygenase-2 (COX-2) inhibition. Besides its potential anti-inflammatory effect, it has been reported that long term administration of nimesulide caused hepatotoxicity in human being. In the present study in order to determine the tissue distribution of nimesulide, the albino rats were administered at a dose rate of 4.5mg/kg body wt. once daily at regular interval through oral route for five days. After five days of dosing blood and tissue samples were collected at predetermined intervals (6,12, 24 and 48hrs). A more sensitive and validated HPTLC analysis method was developed to determine the concentration of this drug in plasma and various tissues such as liver, kidneys, lungs, heart, spleen, and brain. The tissue concentration of nimesulide at 6,12,24 and 48hrs post-administration were compared with plasma concentration. Nimesulide concentration was estimated to be the highest in kidneys at 6,12,24 and 48hrs post administration amongst all tissues examined. The rank order AUC (tissues)/AUC (plasma) ratio was highest for kidney (1.73±0.4) followed by brain, spleen, heart, liver and lungs. The present results suggest that (i) nimesulide concentration during 48hr following withdrawal, declined in a faster rate in plasma and slower rate in tissues like liver,lungs, heart,spleen and brain which accounts about 10-18% of maximal plasma concentration (ii) in kidneys its concentration is maintained at 85% of maximum plasma concentration at 48hr foloowing withdrawal. In conclusion kidney retains a significantly higher concentration of nimesulide upto 2 days following withdrawal of five-day administartion in rats. It is well predicted from the observation obtained from the rat model that (i) kidney damage could be alarming in long term therapeutic administartion to animal and man and (ii) animals and birds could be unsafe consuming the dead animals administered with nimesulide recntly.
Authors and Affiliations
Lombodar Mahapatra , Gayana Sahoo , Monoj Panda , Subas Parija
Keywords
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