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Population Pharmacokinetic Analyses to Evaluate the Influence of Intrinsic and Extrinsic Factors on Exposure of Prasugrel Active Metabolite in TRITON‐TIMI 38
Author(s) -
Wrishko Rebecca E.,
Ernest C. Steven,
Small David S.,
Li Ying G.,
Weerakkody Govinda J.,
Riesmeyer Jeffrey R.,
Macias William L.,
Rohatagi Shashank,
Salazar Daniel E.,
Antman Elliott M.,
Wiviott Stephen D.,
Braunwald Eugene,
Ni Lan
Publication year - 2009
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270009337942
Subject(s) - prasugrel , population , pharmacokinetics , body mass index , renal function , pharmacology , medicine , diabetes mellitus , metabolite , confidence interval , chemistry , endocrinology , environmental health , aspirin , clopidogrel
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 <60 kg (4.1%) was 30% (90% confidence interval [CI] 1.16–1.45) higher than exposure in patients ≥60 kg. Mean Pras‐AM exposures for patients ≥75 years (10.5%) were 19% (90% CI: 1.11–1.28) higher compared with patients <75 years.