Animal Models Test

Using animal models in pharmaceutical research is based on the notion that basic biological processes are sufficiently similar across species so that they can be extrapolated to humans.

The Role of Model Animals

Through the development and utilization of animal models, scientists have been able to make significant strides in improving the health and well-being of both humans and animals, leading to numerous medical breakthroughs and advancements. Animal models that can be used to test drug in vivo are crucial for studying the absorption, distribution, metabolism, and excretion (ADME) of drugs. They are also useful to provide information on toxicity, adverse effects, and drug-drug interactions to ensure the safety of a drug before it enters clinical trials.

Choosing a Model Animal

The selection of animal models can vary depending on the research objectives, with options including homozygous animals, isomorphic animals, and predictive models. Animal models that accurately mimic the disease pathophysiology are extremely useful in characterizing the mechanism of action, pharmacokinetics, pharmacodynamics, toxicity, and efficacy of potential therapies, as well as for human dose prediction in clinical trials. In drug testing, both invertebrate and vertebrate models are utilized. Invertebrate animal models such as zebrafish are commonly used for drug studies involving genetic, neurological, and developmental disorders. Vertebrate models such as mice and rats are important for translational research. The biochemical and physiological similarities between animal models and humans as well as the underlying mechanisms of ADME properties of drugs in the animal are important considerations in the selection of species.

Fig.1 Some animal species have been ingrained as models for specific diseases and areas of study. (Brake, 2017)

• Animal models used in absorption studies
  Drug absorption is mainly influenced by the number and location of drug receptors and the pH of the gastrointestinal tract. Dogs, which are very similar to humans in terms of overall pH changes, are the most commonly used animal models for in vivo absorption studies. Rats and other rodents are more commonly used for the study of pH-sensitive drugs.
• Animal models used in distribution studies
  Carrier-mediated drug transporters in the liver and the extent of efflux through the canalicular membrane are the primary factors that determine drug distribution. Rats and mice are the most prevalent animal models employed for distribution studies.
• Animal models used in metabolism studies
  Drug metabolism studies usually focus on alterations in the activity or expression of metabolizing enzymes. In vivo metabolism studies often emphasize the role of the cytochrome P450 family in the liver, particularly in drug-drug interaction studies. In metabolism studies, animal species such as Rhesus monkeys are frequently utilized because the activity and kinetics of their cytochrome P450 enzymes are similar to those of humans.

Animal Models and Validity

The similarities of disease symptoms and/or disease aetiology in humans and animals is the basis for the development of animal models. A valid animal model is one that closely resembles the human condition in terms of pathogenesis, pathophysiology, symptoms, and response to therapeutic interventions. This validity is typically assessed through three aspects including predictive validity, face validity, and construct validity.

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Reference

1. Brake, K.; et al. In vivo Studies for Drug Development via Oral Delivery: Challenges, Animal Models and Techniques. Pharm Anal Acta. 2017: 2153-2435.