Preclinical Perspective Flashcards
Why do we need animal models?
Ethical and legal reasions againsts human studies without substantial evidence or justification from animal models
Targets
Animal models help to understand the normal physiology and diseases conditions (pathology)
Drug candidates
Animal models are crucial for toxicology studies, dose estimation, efficacy assessments and pharmacology (PK and PD)
Invertebrates
Fruit fly and round worm
Cost effect and no pain
Short life cycle
Great for genetics and pathway dissetions
Mice
Availability Small size Low cost Ease of handling Fast reproduction rate Genetic manipulatability
Non-human primates
Closest to humans
Brains share structural and functional features with human brains
Studies: ID, toxicity, organ transplant
Institutional Animal Care and Use Committee
ID species and number
Complete description of the proposed use of the animals
Procedures designed to assure no discomfort or injury
Strengths of Animal Models
Can control environments, genetics, diet
Independent variables can be manipulated
Gene/genetic approaches can be used to establish functions and targets (cause-effect)
Shorter experimental cycles and less costly
Weakness of Animal Studies
Models do not always correspond to human metabolism and disease
Dose ranges are often extreme and unrealistic for human translation
Routes of exposure and testing not practical for humans
Publication bias in preclinical research
Authors fit new hypotheses to preclinical data
Journal editors through away negative results
Define Allometry
Study of size and its consequences
Huxley & Tessier
Examples of allometry
Dosage does not extrapolate linearly from animals to human based on body weight
Sclaing correctly by metabolic weight and body surface area
Bench to bedside paradigm
Test tube of active compounds and targets
Animal models to establish efficacy and safety, PK/PD, dose
Human clinical trails (Phase 1-3)
Real pts
