Population pharmacokinetic analyses to evaluate the influence of intrinsic and extrinsic factors on exposure of prasugrel active metabolite in TRITON-TIMI 38.

Abstract:

: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 > 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.

journal_name

J Clin Pharmacol

authors

Wrishko RE,Ernest CS 2nd,Small DS,Li YG,Weerakkody GJ,Riesmeyer JR,Macias WL,Rohatagi S,Salazar DE,Antman EM,Wiviott SD,Braunwald E,Ni L

doi

10.1177/0091270009337942

subject

Has Abstract

pub_date

2009-08-01 00:00:00

pages

984-98

issue

8

eissn

0091-2700

issn

1552-4604

pii

0091270009337942

journal_volume

49

pub_type

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