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Updated: Jun 21, 2026

Network Pharmacology Prediction and Metabolomics Validation of the Mechanism of Fructus Phyllanthi against Hyperlipidemia
Published on: April 7, 2023
Prediction of prasugrel active metabolite concentrations from 2 downstream inactive metabolite concentrations using
C Steven Ernest1, Michael A Heathman, Rebecca E Wrishko
1Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. cse@lilly.com
Abstract:
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 substudies. 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 approximately 6% from the unity line and described the variability within approximately 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.
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