Chemotherapeutic agents need to act at a concentration that can be tolerated by the tissues of the host and therefore they must have a selective toxicity for micro organism compared with the host.

This selective toxicity expressed in terms of the “Chemotherapeutic Index” that compress the maximum dose that can be tolerated by the host without causing death (The maximum tolerated dose) with the minimum
dose that cures the particular infection. (minimum curative dose) or the ratio of toxic dosage level to the therapeutic dosage level is termed the chemotherapeutic index defined as the maximum tolerated dose per kilogram of body weight, divided by minimum dose per kilogram body weight that will cure the disease.

Maximum tolerated dose

Chemotherapeutic Index = ------------------------------------------------

Minimum curative does

Chemotherapeutic index provides a rough guide to the degree of selective toxicity value of a chemical, clearly as high a figure as possible is desirable, so that effective therapy may be given without danger of toxicity to the patient.

Anticancer chemotherapeutics are examples of drugs that typically have low chemotherapeutic indices. This is because cancer cells so closely resemble normal body cell that it is difficult to poison the cancer cells without poisoning the body as well.

Broadly useful antibiotics will have a high chemotherapeutic index.

Typically this accomplished by the chemotherapeutic drug attacking a pathogen molecule or metabolic pathway that is not also present in or used by host.

Note that drugs with low chemotherapeutic indices when taken internally may still be acceptable for topical use. Ex: Bacitracin.

Other drugs with low chemotherapeutic indices are still employed because they represent the only drugs available to treat various infections. Ex: Vancomycin.

This index has now been replaced by the “therapeutic index” expressed as the ratio LD50/ED50 Therapeutic index is an approximate assessment of the safety of the drug. It is expressed as the ratio of the median lethal dose to the median effective dose.

LD50

Therapeutic index (TI) = ----------------

ED50

The median lethal dose or LD50

This is the dose (mg/Kg) which would be expected to kill one-half of an unlimited population of the same species and strain.

The median effective dose or ED50

This is the dose (mg/Kg) which produces a desired response in 50% of test population.

Therapeutic index supplies reliable Information when both the LD 50 & ED 50 are determined for the same strain belonging to the same species.

ED50 can be obtained from either quantal or graded dose responsive curve.

The larger the Therapeutic Index, the safer is the drug. Means for safe therapeutic application of a compound, its therapeutic index be more than one.

Eg: Pencillin has a very high therapeutic index smaller for the digitalis preparations.

Generally a drug with a marrow therapeutic range (i.e with little difference between toxic and therapeutic doses) may have its dosage adjusted according to measurements of the actual blood levels achieved in the person taking it.

This may be achieved through therapeutic drug monitoring (TDM) protocols. And minimize toxicity.

Eg: Dimercaprol, Theophylline, Warfarin, Lithium carbonate.

Some antibiotics require monitoring to balance efficacy with minimizing adverse effects.

Ex: Gentamicin, vancomycin, amphotericin B, Polymixin B.