PHARMACOLOGY

 SUBACUTE TOXICITY ::

In this test three doses of drug are administered for a period of one month to 6 months in two species of animals and the effect on various organs are studied One should carry out clinical chemistry physiological signs autopsy studies hematology histology and electron microscopy studies particularly of the target organs of drug producing toxicity Sub-acute toxicity is now a prerequisite for advancing a drug for clinical trial Following is the list of parameters to be included in such studies 

Chronic toxicity ::

These studies are required when the drug is intended to be used in humans for prolonged periods it is usually carried out concurrently with clinical trials The study is carried out in different animal species and the drug is administered for a period of 1-2 years The goal is to find out if any organs are susceptible to drug toxicity in this study clinical chemistry physiological signs autopsy studies hematology histology etc are also carried out in animals as mentioned above 

    As per Schedule Y sub -acute and chronic studies are the Repeated -dose Systemic Toxicity Studies carried out in at least two mammalian species of which has to be a non rodent Dose ranging studies should precede the 14-28-90-or 180-day toxicity studies Duration of the final systemic toxicity study will depend on the duration therapeutic indication and scale of the proposed clinical trial if a species is known to metabolize the drug in the same way as humans it should be preferred for toxicity studies 

    In repeated dose toxicity studies four groups of each gender (total eight groups are required ) one of the 4 groups has to be control receiving either a vehical or distilled water The other three groups have to be low dose (human equivalent dose ) high dose (the dose of the drug that produces observable toxicity but no mortality ) The third dose has to be intermediate of the low and high dose many a time the dose 10 or 20 time may be considered as intermediate or high dose if permissible by the DCGI The drug is administered 7 days a week by the route intended for clinical use To make allowance for the sensitivity of the species the intermediate dose should cause some symptoms but not gross toxicity or death and should be placed logarithmically between the other two doses The number of animais required for these studies are given in the