Animal models variability

Use of in vivo Tests. In vivo tests are more relevant indicators than are in vitro tests of immunotoxicity since the dynamic interactions between the various immuno-components, as well as the pertinent pharmacokinetic (absorption, distribution, plasma concentrations) and metabolic factors, are taken into consideration. However, it is important to select the appropriate animal model and to design the protocol such that it will accurately reflect drug (or relevant metabolite) exposure to humans. For example, one should consider species variability when selecting the animal model, since biological diversity may further obscure the ability to accurately predict human toxicity. 

A major scientific obstacle to the development of a safe and effective vaccine is the difficulty in establishing the precise correlates of protective immunity against HIV infection. A number of factors such as lack of an adequate animal model, lack of incentives, and genetic variability coupled with the relatively poor understanding of the immunologic mechanisms that confer protection have stymied the development of an effective HIV vaccine as of this time. 

Hogg S (1996) A review of the validity and variability of the elevated plus maze as an animal model of anxiety. Pharmacol fiiochem fiehav 54 21-30... 

There exists no scientific basis for the use of animal studies to predict the antitumor effect of a compound however, a fairly good correlation has been shown between the antitumor effects seen in animal studies and those observed in the clinical setting [210], In order to produce an animal model which possesses the requirements listed above, the variable factors present in the experimental procedure, and the characteristics of the tumor and animals must be addressed. 

The number of fresh varieties, dosage forms, and formulations in combination with the variability in botanical material make it impossible to evaluate all of these products in animal models or clinical trials. As a minimum, several products used by the patient community should be obtained and authenticated. The testing and selection criteria should include multiple-lot testing, cost, and product availability, and take into consideration how these products are used. Drug combinations are being examined... 

In order for animal models to be useful, researchers must follow certain practices and methods which will optimize the trans-latability of data from animal models to human affective disorders. Here, we will present a broad review of some reliable methods of analyzing mouse anxiety, and their utility for screening for anxiolytic therapeutic agents. All these tests are of a complex nature and we would suggest that the reader explore each system to better understand the variables and subtleties of each test. We will also discuss how these protocols can be applied correctly, in order to avoid confounding experimental data. 

Because it is necessary for the stroke patient to receive prompt treatment before brain cell death occurs, any useful drug must be effective even when there is considerable time lapse (often several hours) between the occurrence of the stroke and the onset of treatment. The term "therapeutic window" refers to the critical time of intervention between the onset of the ischaemia and occurrence of brain infarction. Some of the drugs that have been developed and shown to be effective in the treatment of various animal models of stroke are listed in Table 14.5. It should be emphasized that none of these drugs is currently marketed for the treatment of stroke. All have been developed on animal models and recent positron emission tomography and magnetic resonance imaging studies have shown that the therapeutic window may be much more variable and prolonged in man than in such models. Only extensive double-blind clinical trials (estimated... 

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