How are toxicology studies conducted

 The branch of pharmacology that deals with the toxic and side effects of new drug molecule is called toxicology. It is also called as preclinical drug safety evaluation. In this study we determine the toxicology of new drug molecule.

If toxicological studies of new drug molecule are not performed then investigational new drug application (INDA) cannot be submitted.

Objectives:

Following are objectives of toxicological studies

      A.    Acute/short term effects

      B.     Long term effects

      C.     Organ specificity

      D.    To determine the site at which toxicity is produce

      E.     Degree of toxicity            

      F.      Relationship between dose and toxic dose

      G.    Effect of drug on gender

      H.    Effect of new drug on reproductive system

      I.       Carcinogenic effect of drug

      J.       Genotoxic effect of drug

      A-    Acute and short term effect:

                                                            To determine acute/short term effects of new drug molecule e.g. when new molecule enter in the body of human/ animal then what are various acute effect produce by a new drug molecule. E.g. Nausea, vomiting, diarrhea etc.

      B-    Long term effect:

To, determine long term effect of a new drug molecule.I.e. when drug is administered to body to which organ is produce damage?E.g. cardio-toxic drug nephrotoxic, hepatotoxic.

Examples:

·         Aminoglycosides cause damage to ear and kidney.

·         Paracetamol cause damage to liver.

·         Some drugs also cause retinopathy.

      C-    Organ specificity:

To, determine the organ specificity of new drug molecule. I.e. in which organ drug is maximally absorbed o maximum concentration of drug is achieve in what organ? Because the organ having maximum concentration of drug also toxicological profile of that organ is maximum I.e. drug produce more side effect of this organ. After drug absorption what is Vd of particular organ because increase in Vd of organ increase the toxicity of drug of that organ.

       D-    To determine site at which toxicity is produce:

Where particular toxicity take place?

Toxicity produces by which mechanism?

Example:

·         If there is GIT drug then it produces side effects on GIT.

·         How this drug cause side effect? On which muscle enzyme is act it may be by inhibiting

·         GIT enzyme by muscle contraction.

Also we determine the exact site on which drug act because GIT is a very long portion. We determine that drug act on small intestine or large intestine or colon to produce side effect.

      E-    Degree of toxicity:

Also we determine the degree of toxicity of new drug molecule, whether it is

·         Acute

·         Chronic

·         Mild

·         Moderate

·         Sever

·         Life threatening

       F-     Relationship between dose and toxic dose:

Also we determine the relation between dose and toxic dose of new drug molecule.

Example: Some drug which have very broad therapeutic index side effect does not appear at high doses. Those drugs which have narrow therapeutic index cause side effect even at low doses.

      G-    Effect of drug on gender:

We also determine the effect of new drug molecule on gender whether it shows toxic effects are more in male female, neonates or geriatrics.

Example:

Cimetidine cause gynecomestia in male but has less effect in females. May be some drugs show effect in one gender but not in other. 

      H-    Effect of new drug on reproductive system:

We also determine the toxic effect of new drug molecule on the reproductive system

      I-       Carcinogenic effect of drug:

To know whether new drug molecule is carcinogenic or not or induce mutation or disturb the gene sequence?

      J-      Genotoxic effect of drug

 What is the effect of new drug molecule on gene sequence or can cause mutation or not?