Overview
Clopidogrel and Ticagrelor were briefly mentioned in Antiplatelet Drugs (from Physiology to Internal Medicine). Today, while studying content related to CHANCE and CHANCE-2, these two drugs were mentioned again, prompting further study.
Both Clopidogrel and Ticagrelor are affected by cytochrome P450 (CYP450), a large family primarily located in the liver.
- CYP2C19 acts on clopidogrel to activate it so that it can inhibit P_2Y_{12}
- CYP3A4 acts on ticagrelor to metabolize it for excretion. If there are liver problems or CYP2C19 issues, clopidogrel cannot be properly activated to exert its antiplatelet effect, and ticagrelor should be used instead.
CYP2C19
CYP2C19 has many alleles:
- CYP2C19-1 is the functional allele mediating CYP2C19 metabolism.
- CYP2C19-2 and CYP2C19-3 are the major alleles causing CYP2C19 enzyme deficiency, which reduce CYP2C19 enzyme activity.
- CYP2C19-17 is an enhanced functional allele that increases CYP2C19 enzyme activity.
If a person mainly has CYP2C19-1, they have normal metabolism. If CYP2C19-2 or -3 predominate, function is impaired. If CYP2C19-17 predominates, function is enhanced.
Some drugs can enhance or inhibit CYP2C19, thereby altering clopidogrel’s effect.
CYP3A4
Ticagrelor does not require activation to exert its antiplatelet effect. CYP3A4 mainly metabolizes it for excretion. When CYP3A4 is inhibited, ticagrelor cannot be properly eliminated, causing blood concentrations to decrease slowly, effectively increasing its efficacy.