After synthesizing/identifying a prospective compound/series of compounds, it is tested on animals to expose the whole pharmacological profile. Experiments are generally performed on a rodent (mouse, rat, guinea pig, hamster, rabbit) and then on a larger animal (cat, dog, monkey).
PRECLINICAL STUDIES
After synthesizing/identifying a prospective compound/series of compounds, it is tested on animals to expose the whole pharmacological profile. Experiments are generally performed on a rodent (mouse, rat, guinea pig, hamster, rabbit) and then on a larger animal (cat, dog, monkey). As the evaluation progresses unfavourable compounds get rejected at each step, so that only a few out of thousands reach the stage when administration to man is considered.
Toxicity tests
The aim is to
determine safety of the compound in at least 2 animal species, mostly mouse/rat
and dog by oral and parenteral routes.
Acute toxicity: Single escalating doses are given to small groups of animals that are observed for
overt effects and mortality for 1–3 days. The dose which kills 50% animals (LD50)
is calculated. Organ toxicity is examined by histopathology on all animals.
Subacute toxicity: Repeated doses are given for 2–12 weeks depending on the duration of intended
treatment in man. Doses are selected on the basis of ED50 and LD50.
Animals are examined for overt effects, food intake, body weight, haematology,
etc. and organ toxicity.
Chronic toxicity: The drug is given for
6–12 months and effects are studied
as in subacute toxicity. This is generally undertaken concurrently with early
clinical trials.
Special longterm toxicity: These tests are
generally performed only on drugs which
cross phase I clinical trials.
Reproduction and teratogenicity: Effects on spermatogenesis, ovulation, fertility and developing
foetus are studied.
Mutagenicity: Ability of the drug to
induce genetic damage is assessed in
bacteria (Ames test), mammalian cell cultures and in intact rodents.
Carcinogenicity: Drug is given for longterm, even the whole life of the animal and they are watched
for development of tumours.
Standardized procedures
under ‘Good Laboratory Practices’ (GLP) have been laid down for
the conduct of animal experiments,
especially toxicity testing.
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