Common diplotypesb | Expected population frequency, %c | PK/PD phenotype | Clinical phenotype | FDA guidelines | ||
---|---|---|---|---|---|---|
Caucasian ancestry | African ancestry | East Asian ancestry | ||||
CYP2C19*1/*1 | 38 | 36 | 35.5 | EM: normal enzymatic function and normal drug activation; normal platelet inhibition | Likely to have a normal response to standard dose of clopidogrel | – |
CYP2C19*1/*2, CYP2C19*1/*8, and other rare diplotypes (see Additional file 1: Table S4) | 19 | 22 | 46 | IM: reduced enzymatic function resulting in reduced drug activation; decreased platelet inhibition | Increased risk of ischemic event while on clopidogrel.d Should use alternative anti-platelet medication | – |
CYP2C19*2/*2 and other rare diplotypes (see Additional file 1: Table S4) | 2 | 3 | 15 | PM: greatly reduced or abolished enzymatic function, leading to little or no drug activation; greatly diminished platelet inhibition | Increased risk of ischemic event while on clopidogrel.d Should use alternative anti-platelet medication | CYP2C19 PMs with ACS or undergoing PCI treated with Plavix at recommended doses exhibit higher cardiovascular event rates than do patients with normal CYP2C19 function. Consider alternative treatment or treatment strategies in patients identified as CYP2C19 PMs |
CYP2C19*1/*17, CYP2C19*17/*17 | 34 | 31 | 2 | UM: enhanced enzymatic function leading to greater drug activation | Possible increased risk of bleeding; but also likely to derive greater protection from ischemic event while on clopidogrel | – |
CYP2C19*2/*1 7 and other rare diplotypes (see Additional file 1: Table S4) | 7 | 8 | 1.5 | Unk: metabolizer status undetermined and therefore unknown. PD data indicates platelet response is intermediate between likely IMs and EMs | Unknown effect on drug response | – |