Question3. What is the main reason that pre-clinical study should be performed before the clinical one?

Pre-clinical development is a stage before clinical trials (testing in humans) can begin, and during which important safety and pharmacology data is collected.

The main reason that preclinical studies should be performed before clinical studies is that this information helps to start safe human testing.

The main goals of pre-clinical studies (also named preclinical studies and nonclinical studies) are to determine a drug’s pharmacodynamics (PD),pharmacokinetics (PK), ADME, and toxicity through animal testing. This data allows researchers to allometrically estimate a safe starting dose of the drug forclinical trials in humans. Pre-clinical studies must adhere to Good Laboratory Practices (GLP) in ICH Guidelines to be acceptable for submission to regulatory agencies such as the Food & Drug Administration in the United States .

Typically, both in vitro and in vivo tests will be performed. Studies of a drug’stoxicity include which organs are targeted by that drug, as well as if there are any long-term carcinogenic effects or toxic effects on mammalian reproduction.

The choice of species is based on which will give the best correlation to human trials. Differences in the gut, enzyme activity, circulatory system, or other considerations make certain models more appropriate based on the dosage form, site of activity, or noxious metabolites. For example, canines may not be good models for solid oral dosage forms because the characteristic carnivore intestine is underdeveloped compared to the omnivore’s, and gastric emptying rates are increased. Also, rodents can not act as models for antibiotic drugs because the resulting alteration to their intestinal flora causes significant adverse effects. Depending on a drugs functional groups, it may be metabolized in similar or different ways between species, which will effect both efficacy and toxicology.

Pre-clinical studies include a wide range of studies in a variety of systems to characterize biopharmaceutic and pharmacokinetic properties. Systems used include: in vivo animal models, isolated perfused liver, kidney, intestine, hind limb and heart, Caco-2 cell monolayer absorption model, animal and human liver microsomes. Studies include: bioavailability studies, pharmacokinetic studies, prediction of oral absorption in humans, determination of mechanisms of intestinal absorption, assessment of transport, distribution and elimination of compounds, validated models for cytochrome P450 enzymes, metabolism studies in human liver microsomes, assessment of potential for metabolic drug – drug interactions, analysis of drugs and metabolites in biological matrices, synthetic chemistry, in silico modeling.

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