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Animal studies were done using an in vivo dogmodel to examine the possible mechanism for theesophageal adverse events reported with alendronatesodium tablets. These studies showed that under low pHconditions alendronate sodium can cause esophagealirritation. No esophageal irritation occurred at pH 3.5or higher where the drug exists primarily as the(More)
Alendronate (4-amino-1-bydroxybutylidene bisphosphonate) is a novel amino bisphosphonate that is being developed for the treatment of osteolytic bone disorders such as osteoporosis. As part of a 2-year carcinogenicity study, we investigated the morphologic and biomechanical effects of long-term alendronate (ALN) therapy, given throughout skeletal growth,(More)
Bisphosphonates have generally few clinicaladverse effects, the most common being gastrointestinaldisturbances. It is generally believed thatbisphosphonates with a primary amine are more irritatingto the gastrointestinal tract than those withouta primary amine. The objective of this study was tocompare the gastric irritation potential of an(More)
Alendronate is a bisphosphonate which inhibits bone resorption. In female fertility studies in rats, dosages of 10 and 15 mg/kg/day produced physical signs of toxicity at parturition, including tremors, dystocia, and death in the dams and these were associated with neonatal deaths. These effects were associated with hypocalcemia in the dams but the fetuses(More)
The objective of this study was to determine the effects of 2 different 5-alpha reductase inhibitors (finasteride and MK-0434) on the glandular and stromal compartments of hyperplastic canine prostates. In this study, dogs received 1 of the 2 compounds orally, at a dose of 1 mg/kg/day for 16 weeks; control dogs received a placebo. The morphological changes(More)
Young mature dogs received finasteride, a selective 5 alpha-reductase inhibitor, orally at 0, 5, 15, and 45 mg/kg/day for 27 or 53 weeks. The effect of finasteride administration on prostatic size and morphology was evaluated macroscopically and microscopically. Changes in glandular and fibromuscular compartments were quantitated by a point counting method(More)
Lovastatin, a specific inhibitor of the rate-limiting enzyme in cholesterol biosynthesis, HMG-CoA reductase, has been shown to be highly effective in lowering serum cholesterol in animals and humans and thus represents a promising approach to the treatment and prevention of cardiovascular disease. During the preclinical safety assessment of lovastatin, oral(More)
Female rats were administered lead (Pb), as the nitrate salt, on day 17 of pregnancy (5 or 25 mg/kg i.v.) or throughout lactation (5 or 25 mg/kg/day p.o.). There were adverse effects on weights of females receiving Pb on day 17. At 25 mg/kg i.v. gestation was significantly prolonged. In both groups treated intravenously, average pup weight on day 1(More)