Q28 - CYP2C19 Polymorphisms and Drug Metabolism of Omeprazole and Clopidogrel

Theoretical 2 Real exam question - full text reproduced under IBO's CC BY-NC-SA 4.0 license

Digestive & Metabolic Physiology Population Genetics & Hardy-Weinberg Equilibrium

CYP2C19 belongs to the cytochrome P450 family of enzymes expressed in the liver for detoxification. It metabolizes and inactivates various drugs, but single nucleotide polymorphisms (SNPs) in CYP2C19 (denoted 1*, 2*, 3*) have different allele frequencies among populations: Sweden (69.4%, 27.8%, 2.7%), France (56.7%, 37.2%, 6.1%), China (38.2%, 47.2%, 14.6%), Japan (27.7%, 49.9%, 22.5%) for *1, *2, *3 respectively. Genotype *1/*1 = Extensive metabolizer; *1/*2 or *1/*3 = Intermediate metabolizer; *2/*2, *2/*3, or *3/*3 = Poor metabolizer. Omeprazole (for gastric ulcer/reflux) is metabolized (inactivated) by CYP2C19. Clopidogrel (for preventing myocardial/cerebral infarction) is also metabolized by CYP2C19, but in this case the metabolite itself is the active drug that inhibits its platelet-surface target.

Using the information and data, determine which of the statements are true or which are false.

A. Orally administered drugs absorbed in the intestinal epithelium are first transported to ___.

B. What is the order of genotypes for the effect of omeprazole from the most long-lasting to the shortest-lasting effect after oral administration?

C. Which countries have the highest proportion of patients for whom omeprazole works well?

D. If clopidogrel does not show sufficient effect due to the CYP2C19 SNPs in the patient, what is expected by combining omeprazole with clopidogrel on the effectiveness of the clopidogrel?

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