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- The protective index is a comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes toxicity. Quantitatively, it is the ratio given by the toxic dose divided by the therapeutic dose. A protective index is the toxic dose of a drug for 50% of the population (TD50) divided by the minimum effective dose for 50% of the population (ED50). A high protective index is preferable to a low one: this corresponds to a situation in which one would have to take a much higher dose of a drug to reach the toxic threshold than the dose taken to elicit the therapeutic effect. A drug should ordinarily only be administered if the protective index is greater than one, indicating that the benefit outweighs the risk. The protective index is similar to the therapeutic index, but concerns toxicity (TD50) rather than lethality (LD50); thus, the protective index is a smaller ratio. Toxicity can take many forms, as drugs typically have multiple side effects of varying severity, so a specific criterion of toxicity must be specified for the protective index to be meaningful. Ideally a choice is made such that the harm caused by the toxicity just outweighs the benefit of the drug's effect. Thus, the protective index is a more accurate measure of the benefit-to-risk ratio than the therapeutic index, but is less objectively defined. Nevertheless, the therapeutic index can be viewed as an upper bound to the protective index for a given substance. Protective IndexProtective index refers to the factor by which thedose of a toxicant must be multiplied to produce adefined level of toxicity in the presence of a nontoxicdose of another chemicalBhat et al., 2007. 'Protective index = LD50 of A with B/LD50 of A alone' The higher the protective index, better is theantidotal value of a given substance. Sometimes theprotective index is higher in the presence of two ormore substances than in the presence of either of thesubstances alone. For example, the LD50 of potassiumcyanide alone is 11 mg/kg, whereas it is 21 mg/kgin the presence of sodium nitrite, giving a protectiveindex of 1.91. The LD50 of potassium cyanide in thepresence of sodium thiosulfate is 35 mg/kg, givinga protective index of 3.2. The LD50 of potassiumcyanide in the presence of both nitrite and thiosulfateis 52 mg/kg with a protective index of 4.73 . Since the protective index is higher forthe simultaneous use of nitrite and thiosulfate, thetwo chemicals constitute the antidote against cyanideintoxication. Bhat, A Shakoor and Ahanger, Azad A, 2007. Toxicology Mechanisms and Methods, 17:441–450, 2007
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