Cardiovascular disease safety testing

Since heparin protected the animals from histamine toxicity in a dose-response, it was thought to be safe to use in human patients for clinical trial. Heparin had of course been used in cardiovascular disease in large doses for many years. It was believed that there would be safety as long as the dosage was kept within the half gram used in cardiovascular disease. Further, since heparin was bound by histamine in the animal studies, it was believed that it would not be free in the blood to cause bleeding difficulties. Lee-White tests were performed on many of the patients and confirmed this finding. 

Major Applications Sensors, - photoconductors, copying materials, rubber, 3- 5 body fluid testing, determination of calcium, magnesium, tin, method for measuring urea nitrogen, liposomal construct for diagnostic use, cardiovascular disease, antibacterial agent Safety/Toxicity In vitro toxicity ... 

Another potential use for these drugs was to prevent the formation of adenomatous polyps in patients with a history of colorectal adenomas. Rofecoxib and celecoxib were both tested in this disease. It was the results of this test that prompted Merck to withdraw their drug from the market since this study clearly established the increased risk of cardiovascular events when rofecoxib is used. The results were sufficiently strong to have the safety monitoring board reevaluate the data for a similar trial with celecoxib. On the basis of these data the study with celecoxib was also terminated. Interestingly, another study in which celecoxib was used to prevent polyp formation resulted in no increase in cardiovascular events. The only difference between the two studies was that in the latter case celecoxib was given once a day whereas in the prior study celecoxib was administered at the same dose but twice a day. How this difference in treatment schedules affected the toxic outcomes is unknown at the present time. 

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