Dosage significance

Fig. 9.5. Protection by SERMs against atherosclerosis has been researched in animals. In a model of ovariectomized rabbits, raloxifene reduced the cholesterol content in the inner part of the aorta more than placebo did (upper panel). This effect was more intense in animals treated with estradiol (Bjarnason et al. 1997). In contrast, in a different model of oophorectomized monkeys (lower panel), estradiol, and not raloxifene at two different dosages, significantly decreased the size of atherosclerotic plaques (Clarkson et al. 1998)...

Niacin benefits heart health when used at dosages significantly higher than when the vitamin is viewed in nutritional terms. It works its wonders in the liver, the principal site of cholesterol manufacture by the body. As such, niacin usage should be monitored by your physician. Regular tests will determine not only your cholesterol levels but also the health of your liver. Be sure to discuss this with your doctor. He or she will certainly be aware of just how well niacin works as your heart s best friend. If not, point your doctor to the references cited at the end of this book. 

The mechanism by which sucralfate accelerates healing of duodenal ulcers has not been determined. It does not have significant antisecretory, acid neutralizing activity or direct stimulation of ulcer healing. It is known that the mechanism is local rather than systemic. Binding of pepsin or bile salts may contribute to its effect. It is indicated for the short-term therapy of active duodenal ulcers and for maintenance at reduced dosage. 

PhRMA is a trade association of over 100 research-based pharmaceutical companies. For membership a company must manufacture and market finished dosage-form products under its own brand names and must conduct a significant amount of research and development in the United States. 

Polydioxanone (PDS) is completely elirninated from the body upon absorption. The mechanism of polydioxanone degradation is similar to that observed for other synthetic bioabsorbable polymers. Polydioxanone degradation in vitro was affected by gamma irradiation dosage but not substantially by the presence of enzymes (39). The strength loss and absorption of braided PDS, but not monofilament PDS, implanted in infected wounds, however, was significantly greater than in noninfected wounds. 

Intracerebroventricular injection of sulfolane in dosages of 300, 1000, and 3000 p.g caused the preoptic/anterior hypothalamic area temperature to rise 0.23, 0.47, and 0.56%, respectively. This hyperthermia was considered significant at the 3000-p.g dosage (30). 

Because some patients are more sensitive to side effects with digoxin, the dosage is selected carefully and adjusted as the clinical condition indicates. Adverse reactions were more common and severe in past years before careful attention to weight, renal function, and the concurrent administration of certain medications was given. The incidence and severity of digoxin toxicity has decreased significantly in recent years. 

During die ongoing assessment die nurse monitors the blood pressure, pulse, and respiratory rate every 4 hours or as ordered by the primary healtii care provider. The primary health care provider is notified if tiiere are any significant changes in tiiese vital signs because a dosage adjustment may be necessary. 

The drug should be administered at three levels by the route proposed for humans. The high dose level should be set so as to have relevance in humans. For drugs that display significant toxic effects, this may be related to the maximally tolerated dose in the toxicity tests, for example, the dose causing less than 10% deviation in body weight versus controls. If there is little evidence of toxicity it may be more appropriate to base the dose level on a multiple (usually 25-fold) of the maximum therapeutic dosage recommended in humans. 

Efficacy Supplement = submissions for such changes as a new indication or dosage regimen for an approved product, a comparative efficacy claim naming another product, or a significant alteration in the patient population e.g., prescription to Over-The-Counter switch ... 

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