J Clin Pharmacol
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 QUICK SEARCH:   [advanced]


     

Sign In to gain access to subscriptions and/or personal tools.
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
0091270009337942v1
49/8/984    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Google Scholar
Right arrow Articles by Wrishko, R. E.
Right arrow Articles by Ni, L.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wrishko, R. E.
Right arrow Articles by Ni, L.
Social Bookmarking
 Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

PHARMACOKINETICS

Population Pharmacokinetic Analyses to Evaluate the Influence of Intrinsic and Extrinsic Factors on Exposure of Prasugrel Active Metabolite in TRITON-TIMI 38

Rebecca E. Wrishko, PhD, C. Steven Ernest, II, MS, David S. Small, PhD, Ying G. Li, MS, Govinda J. Weerakkody, PhD, Jeffrey R. Riesmeyer, MD, William L. Macias, MD, PhD, Shashank Rohatagi, PhD, Daniel E. Salazar, PhD, Elliott M. Antman, MD, Stephen D. Wiviott, MD, Eugene Braunwald, MD and Lan Ni, PhD

From Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana (Dr Wrishko, Mr Ernest, Dr Small, Ms Li, Dr Weerakkody, Dr Riesmeyer, Dr Macias, Dr Ni); Daiichi Sankyo, Inc, Parsippany, New Jersey (Dr Rohatagi, Dr Salazar); and TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts (Dr Antman, Dr Wiviott, Dr Braunwald).

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.


Key Words: Population pharmacokineticsmaximal platelet aggregationprasugrelTRITON-TIMI 38

Address for reprints: Rebecca Wrishko, PhD, Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285; e-mail: wrishkore{at}lilly.com.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?





HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2009 by the American College of Clinical Pharmacology