Principle : The pre-clinical trials provide the items of information whose knowledge is deemed necessary prior to the implementation of a first administration in humans.
in addition to analytical data and dosage that will be included in the pharmaceutical dossier of the dossier for marketing authorisation (authorisation of the placing on the market), this is a pre-requisite toxicological and pharmacological properties that are sought after. the framework of these pre-requisite has been defined by the ich or international conference of harmonization www.ich.org, which is held every two years to supplement or replace the formal requirements of the united states, the european union and japan.
- Acute toxicity or single-dose: The acute toxicity is intended to determine the toxic doses in animals and the bodies with selectively of this toxicity.
- Chronic toxicity or dose repeated: The chronic toxicity is intended to obtain information on the ability of the product to accumulate in the tissues and to confirm which organs suffer selectively from this toxicity.
- Reproductive functions: These studies aim to assess the impact of the product on fertility and on pregnancy.
- Mutagenesis / Genotoxicity: Mutagenesis objective is to detect modifications of the genetic material induced by the drug (mutagenic or clastogenic), that this is a cancer risk for the current generation or a genetic risk for future generations.
- Carcinogenesis: This step allows to detect a possible carcinogenic potential of the product. these studies may be conducted in parallel studies of first-in-human, except in the case of call signs (ex : tests of mutagenesis positfs).
- Pharmacodynamics: These studies consist of a battery of tests using in vivo models and in vitro to distinguish between:
– the effects specific to the molecule (pharmacodynamics specific) with evidence of a relationship dose effect and effect-time, the determination of the ed50 (effective dose 50, or dose causing 50% of maximum effect) is always expressed in mg/kg, and research of the mechanism of action of the
– the general effects
– the possible interactions.
- Pharmacokinetics: This is the fate of the molecule in the body which one distinguishes in general 4 phases named « adme » for : absorption, distribution, metabolism and elimination.
It needs to be studied in animals using the route of administration is most appropriate given the clinical route of administration and should be carried out before the tests of phase i.