Question

The drug Plavix requires the enzyme CYP2C19 to take it from the prodrug form to the drug form (enzyme A below) and it requires the enzyme CES1 to convert it from active to inactive (enzyme 1 below). The active form of the drug is effective in preventing blood clots but is toxic in higher doses. Individuals with a mutation in the CYP2C19 gene produce a version of CYP2C19 that is 50%less effective. You are a physician trying to determine the dosage of Plavix for a patient who is homozygous for the mutated version of the CYP2C19 gene. What should you do?
Prodrug ? Drug ? Inactive Drug
Enzyme A Enzyme 1

A. Decrease the normal dosage because they are making too much of the toxic endproduct

B. Increase the normal dosage because they are making too much of the toxic endproduct

C. Increase the normal dosage because they are not making enough of the drug

D. Decrease the normal dosage because they are making too much of the drug

Answer 1

Answer C: The physician has to increase the normal dosage because the patient is not making enough of the drug. The patient is homozygous for the mutated version of the gene CYP2C19 which means that the patient has both the alleles for CYP2C19 defective and cannot make 100% of this enzyme. In this case, very less of the prodrug gets converted into the active drug and the chances of toxicity at higher doses of the prodrug are very less. Thus, if the normal dosage is increased to meet the needs of the patient then enough prodrug can be converted into the drug form by the CYP2C19 enzyme which is already underperforming or less efficient or mutated in scientific terms. I hope that’s helpful.