What intrinsic and extrinsic factors influence the exposure of prasugrel's active metabolite in patients from TRITON-TIMI 38?
Prasugrel active metabolite exposure is significantly higher in patients weighing <60 kg and those aged ≥75 years, supporting potential dose adjustments in these subgroups.
Serial pharmacokinetic (PK) sampling in 1159 patients from TRITON-TIMI 38 was undertaken. A multilinear regression model was used to quantitatively predict prasugrel's active metabolite (Pras-AM) concentrations from its 2 downstream inactive metabolites. Population-based methods were then applied to Pras-AM concentration data to characterize the PK. The potential influence of body weight, body mass index, age, sex, renal function, diabetes, tobacco use, and other disease status on Bayesian estimates of Pras-AM exposures was assessed. The PK of Pras-AM was adequately described by a multicompartmental model and consistent with results from previous studies. The systemic exposure of prasugrel was not appreciably affected by body mass index, gender, diabetes, smoking, and renal impairment. Pras-AM mean exposure in patients weighing or =60 kg. Mean Pras-AM exposures for patients > or =75 years (10.5%) were 19% (90% CI: 1.11-1.28) higher compared with patients <75 years.
Wrishko et al. (Tue,) studied this question.