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Question A2 Both Drug A and Drug B produce similar therapeutic effect for treatment of cardiac...

Question A2 Both Drug A and Drug B produce similar therapeutic effect for treatment of cardiac arrhythmias. The ED50 and TD50 of Drug A are 200mg and 1g respectively, whereas the ED50 of Drug B is 250mg with a TD50 of 2g.

(a) Calculate the therapeutic index (TI) of these two drugs.

(b) Determine which drug is safer for administration and clearly explain your answer.

Solutions

Expert Solution

ED50 is the dose effective in 50% of individuals or populations.

TD50 is the dose that produces toxic effects in 50% of individuals or populations.

Therapeutic index (TI): is a comparison of the amount of a drug that produces the therapeutic effect to the amount that causes toxicity. It is a ratio of TD50 to ED50.

TI=TD50/ED50

For drug A,

TI = 1000/200 =10

For drug B,

TI= 2000/250 = 8

The therapeutic index is also commonly known as the safety window or therapeutic window.

Greater the TI safer is the drug because toxic effects of dose are only seen after the drug is administered at TI fold concentration. This means if the TI of the drug is 10, this indicates that toxic effects produced in the 10 fold of effective dose.

Hence, Drug A with TI 10 is safer than Drug B with TI 8.

Moreover, the use of ED50 and TD50 to derive the TI is not appropriate and mislead about a drug's safety, depending on the slope of the dose-response curves for TD and ED.

The toxicologists often use the Margin of Safety to denote the safety of a drug.

The margin of safety is usually calculated as the ratio of the toxic dose to 1% of the population (TD01) to the dose that is 99% effective to the population (ED99).


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