Animal models advantages

For a number of liposome preparations—both injectables and locally administered products—the therapeutic advantages over existing formulations have been proven in animal models clinical trials with liposome preparations are now under way. So far, clinical studies showed no significant toxic effects which could be ascribed to the lipid components of the liposomes used. 

Hypertonic sahne is actively excluded from an intact BBB and also acts to draw water into the intravascular space by the creation of a sodium gradient. Various concentrations have been evaluated, with continuous sodium chloride infusions ranging from 3% to 9%, and bolus infusions up to 23.4% administered over 20 minutes in a 30 mL solution. When a continuous infusion is used, the serum sodium is typically titrated to the 155-160 range. Sodium levels above this range raise the concern for seizures and other toxic side effects. Hypertonic saline may hold an advantage over mannitol, as it has been found in animal models to decrease edema in both... 

There are three generally accepted criteria for validating animal models for human psychiatric disorders face validity, construct validity, and predictive validity. Face validity refers to the outward appearance of the model, i.e. does the animal s behavior adequately reflect the human behavior being modeled In this dimension, anxiety models have a clear advantage over other psychiatric models it is usually quite apparent if an animal is frightened, whereas it is a much more difficult to assess whether an animal is displaying psychotic-like or depressive-like behavior, for example. 

Reasons for chopping clinical candidates at any stage of the drug approval process included (1) stability, formulation, or other pharmaceutical development issues, (2) renal toxicity or neurotoxicity, and (3) insufficient advantage over current chugs. Since 1997, the NCI has also operated a screen for compounds active against the cytotoxic effects of HIV in CEM cells. Of 80,000 compounds tested, 4050 (or about 5%) were active. Of the compounds tested, 2291 have included metals. Of those, 136 (about 6%) were active, and two became clinical candidates. Both were chopped due to toxicity problems. One clinical candidate was a polyoxometallate, and therefore about 80 other similar molecules were tested. These were found to be strongly active in vitro, but too toxic in animal models in vivo. If a way around the toxicity problem can be found, interest in these... 

With the aim of developing animal models appropriate for safety assessment of allergenic potential a number of species has been considered, including swine [94,99] and dogs [94,100-102], Although these species have their advantages, discussion here... 

Local administration of NO to the lungs has been shown to reverse pulmonary hypertension in animal models [103], importantly with no systemic side effects. This is likely to be as a result of surplus NO being removed as nitrosyl-hemoglobin [104]. Such advantages of gaseous NO were first reported in 1991 [105, 106]. In 1999 and 2001 NO gas was approved as a drug in the USA and European Union, for treating hypoxemic respiratory failure in infants [107]. 

This section is devoted to the definition and comparison of the three nonrodent animal models (dog, ferret, and monkey) in terms of experimental procedures, environmental and dietary requirements, as well as advantages and disadvantages of use in safety assessment testing. 

Advantages and Disadvantages. Advantages of using monkeys in safety assessment studies include their phylogenetic proximity, as well as their physiological, behavioral, and, often, metabolic similarities, to humans (Table 16.13). An example is the similarity between the ovarian cycle of female monkeys and women (Mazue and Richez, 1982), which makes the monkey the ideal animal model for reproductive studies. Another advantage associated with most species of monkeys used in safety assessment studies is that they are much smaller than nonrodents such as the dog and, thus like the ferret, require less test compound. 

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