Laboratory Animals in Pharmacology

Introduction & rationale

• Experimental pharmacology — studies drug action at the level of the whole animal, isolated organ or tissue; the laboratory animal is the substrate on which pharmacodynamic, pharmacokinetic and toxicological hypotheses are tested before human exposure.
• Where it fits in drug development — animals dominate the Stage II preclinical phase — in vitro and in vivo pharmacodynamics, pharmacokinetics and acute/chronic/genotoxicity testing that derives the maximum recommended starting dose (MRSD) used to set the safe starting dose for first-in-human trials.
• Why animals are used — an animal model tests possibilities "difficult or impossible" to test in humans, valid when two species strongly resemble each other for the specific system studied; over 200 years of such work underlies our understanding of drug action.
• Historical anchors — Magendie & Claude Bernard founded experimental animal physiology/pharmacology; Lavoisier used a guinea pig to prove respiration is combustion; Pasteur demonstrated the germ theory by giving anthrax to sheep.