In a chiral drug with active S-enantiomer, why might total plasma concentration fail to predict effect?

In a chiral drug with active S-enantiomer, why might total plasma concentration fail to predict effect?

• A. Only one enantiomer is active; total concentration includes inactive enantiomer
• B. Both enantiomers are equally active
• C. Enantiomers are not enantiomer-specific
• D. Total plasma concentration always predicts effect

Answer: (A)

When the drug is chiral and one enantiomer drives the therapeutic effect, the response depends on the concentration of that active enantiomer at its site of action, not the total amount of both enantiomers. If only the S-enantiomer is active, the total plasma concentration includes the inactive R-enantiomer, which can misrepresent how much pharmacologically active drug is available to produce the effect. This is why total plasma levels may not predict the actual pharmacodynamic response. The other statements don’t fit because: if both enantiomers were equally active, total concentration would be a better surrogate for effect; enantiomers can indeed differ in activity (they are often enantioselective); and saying total concentration always predicts effect ignores the possibility of enantioselective activity.

When the drug is chiral and one enantiomer drives the therapeutic effect, the response depends on the concentration of that active enantiomer at its site of action, not the total amount of both enantiomers. If only the S-enantiomer is active, the total plasma concentration includes the inactive R-enantiomer, which can misrepresent how much pharmacologically active drug is available to produce the effect. This is why total plasma levels may not predict the actual pharmacodynamic response.

The other statements don’t fit because: if both enantiomers were equally active, total concentration would be a better surrogate for effect; enantiomers can indeed differ in activity (they are often enantioselective); and saying total concentration always predicts effect ignores the possibility of enantioselective activity.