Authors : Ibraheem A. Al-Omar, Riyadh M. Al-Ashban and Arif H. Shah
Abstract: Concerns about quality of a drug product and its maintenance during the shelf life is voiced by many health authorities. Usually the degradation products of a drug lead to toxicity and/or unexpected clinical results. 4-Chloro-5-Sulfamoylanthranilic Acid (CSA) is the major degradation product of the well established loop diuretic Furosemide (FM). Acute, subacute and chronic toxicity studies were conducted on CSA and the parent drug FM for comparison using mice as experimental model. General toxicity symptoms, body weight changes, effect on vital organs, hematological and biochemical changes and effects on the bone marrow cells were recorded following established experimental protocols. In each case, the results obtained were sustanciated by histopathological investigations. During acute treatment, FM 100 mg kg-1 dose significantly increased the levels of AST, creatinine and urea, while CSA treatment caused increase only in AST and creatinine levels. FM treatment induced clastogenic effect p<0.05 on the femoral cells of mice. In subacute study, both CSA and FM treatment significantly increased (p<0.001) AST and ALT levels. In addition, CSA treatment significantly reduced glucose levels as well. There were no appreciable changes in hematological indices during acute treatment. However, subacute and chronic treatment with CSA higher dose, caused significant changes in hematological and biochemical indices. No clastogenic activity was observed during subacute and chronic toxicity studies. Mortality rate was found higher in FM higher dose treatment group in both subacute and chronic toxicity studies. Histopathological investigations after acute treatment revealed inflammatory change and congestion in liver of mice; while only mild congestion in heart and kidney were also noticed. Histopathological studies on CSA treated mice after subacute and chronic treatment induced interesting changes. The over all results of current study shown CSA to possess toxic potential.
Ibraheem A. Al-Omar, Riyadh M. Al-Ashban and Arif H. Shah, 2009. Toxicity Studies on 4-Chloro-5-Sulfamoylanthranilic Acid the Degradation Product of a Loop Diuretic Furosemide. Research Journal of Pharmacology, 3: 63-77.