Abstract 10678: Pharmacokinetic and Pharmacodynamic Effects of Prasugrel and Clopidogrel According to CYP2C19 Genotype in Very Elderly and Non-Elderly Patients With Coronary Artery Disease
Background: In non-elderly (NE) (≥45 to <65 yrs) patients, CYP2C19 genotype has been reported to influence the response to clopidogrel (Clop) but not prasugrel (Pras). A Pras 5 mg/d dose in very elderly (VE) patients (≥75 years old) is recommended based on pharmacokinetic (PK) and pharmacodynamic (PD) modeling, but prospective data in the VE are lacking. The GENERATIONS study is a blinded, randomized cross-over study comparing the PK and PD effects of Pras (5 mg qd), Pras (10 mg qd) and Clop (75 mg qd) in NE and VE patients with stable CAD.
Methods: In the current analysis, active metabolite PK (AUC) and PD effect (LTA [20uM ADP], VerifyNow P2Y12 and VASP assays) were analyzed according to CYP2C19 genotype: reduced metabolizers (RM: loss-of-function allele carriers) and extensive metabolizers (EM: non-carriers).
Results: Pras PK at 5 mg qd (pint=0.27) and 10 mg qd (pint=0.75) were not influenced by genotype irrespective of age whereas Clop PK were lowered in RM and this finding was not influenced by age (pint=0.59; Table). Clop PD effect was lower in RMs vs. EMs (p<0.025 for all assays) irrespective of age (pint≥0.37 for all assays, data not shown). VE patients treated with Pras 5 mg qd (RMs + EMs) showed greater PK and PD effects (LTA 20uM ADP) than EMs treated with 75 mg qd Clop (p≤0.007 for both, data not shown).
Conclusions: In contrast to Clop, the PK of Pras at either dose is not influenced by CYP2C19 genotype in either population (NE and VE). Pras 5 mg qd in the overall group (RMs + EMs) of VE patients provides a greater PD effect than Clop 75 mg qd in VE EMs.
- © 2012 by American Heart Association, Inc.