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Prediction of Prasugrel Active Metabolite Concentrations From 2 Downstream Inactive Metabolite Concentrations Using Multilinear Regression Analysis
Author(s) -
Ernest C. Steven,
Heathman Michael A.,
Wrishko Rebecca E.
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 - 10.1177/0091270009340416
Subject(s) - prasugrel , metabolite , thienopyridine , chemistry , active metabolite , pharmacology , medicine , biochemistry , aspirin , clopidogrel
Prasugrel is a thienopyridine prodrug that is metabolized to an active metabolite (Pras‐AM), which inhibits adenosine diphosphate (ADP)–induced platelet aggregation. The study objective was to describe a multilinear regression correlation model that was used to quantitatively predict concentrations of Pras‐AM from downstream inactive metabolites, R‐119251 and R‐106583, for the purpose of estimating Pras‐AM exposure in patients in the TRITON‐TIMI 38 sub‐studies. The model development included 1462 Pras‐AM, 1345 R‐119251, and 1456 R‐106583 concentration data points from 103 healthy participants with a prasugrel dose range of 15 to 80 mg. The model was shown to provide good correlation between predicted and observed concentrations with only a minor deviation of ∼6% from the unity line and described the variability within ∼4.5%. Examination of the data indicated that regardless of ethnicity, age, weight, moderate hepatic impairment, or renal impairment, predictions were reliable. Predicted Pras‐AM concentrations in TRITON‐TIMI 38 were comparable with historical data.