Prediction of prasugrel active metabolite concentrations from 2 downstream inactive metabolite concentrations using multilinear regression analysis.
J Clin Pharmacol
; 49(8): 973-83, 2009 Aug.
Article
em En
| MEDLINE
| ID: mdl-19602721
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piperazinas
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Tiofenos
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Inibidores da Agregação Plaquetária
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Modelos Biológicos
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Adolescent
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Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Clin Pharmacol
Ano de publicação:
2009
Tipo de documento:
Article