Safety pharmacology animal disease models

Milano, S., Introducing disease animal models in safety pharmacology a way to reevaluate the risk, MDS Sifety Pharmacology Symposium, Lyon, France MDA Pharma, December 5-6,2002. 

In addition to toxicity and safety data, the preclini-cal package to start clinical studies also contains information on the pharmacology, the pharmacokinetics and metabolism and the galenical aspects of the compound. As a rule there is evidence of pharmacological activity and, if possible, of therapeutic activity in one or more animal models of disease. Ideally there is also information on the in vivo concentration effect relationship. 

Studies should be designed in a relevant model. Consideration should be given to the usefulness/ability of existing models to (1) mimic the disease/human population (activity/efhcacy) and (2) predict safety (toxicity) in the context of the similarity in anatomy and pathophysiology. A discussion of whether the disease status of the animal has an impact on pharmacologic/toxicologic activity and whether the investigative therapy has an impact on the disease status of the animal should be provided. 

These models may provide further insight, not only in determining the pharmacological action of the product, pharmacokinetics, and dosimetry, but may also be useful in the determination of Safety (e.g., evaluation of rmdesirable promotion of disease progression). In certain cases, studies performed in animal models of disease may be used as an acceptable alternative to toxicity studies in normal animals Note 1). The scientific justification for the use of these animal models of disease to support safety should be provided. 

---