The influence of body size on the pharmacodynamic and pharmacokinetic response to clopidogrel and prasugrel: A retrospective analysis of the FEATHER study
| Autor: | Brian A. Moser, Kenneth J. Winters, Joseph A. Jakubowski, Stefan James, David Erlinge, Patricia B. Brown, Dominick J. Angiolillo, Chunmei Zhou, David S. Small, Jurriën M. ten Berg |
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| Rok vydání: | 2014 |
| Předmět: |
Adult
Blood Platelets Male medicine.medical_specialty Ticlopidine Prasugrel Platelet Aggregation Platelet Function Tests Thienopyridine Body Surface Area Coronary Artery Disease Loading dose Body Mass Index Pharmacokinetics Internal medicine medicine Body Size Humans Drug Dosage Calculations Aged Randomized Controlled Trials as Topic Retrospective Studies Platelet-poor plasma Body surface area business.industry Body Weight Microfilament Proteins Hematology Middle Aged Phosphoproteins Clopidogrel Receptors Purinergic P2Y12 Treatment Outcome Endocrinology Anesthesia Purinergic P2Y Receptor Antagonists Female business Cell Adhesion Molecules Prasugrel Hydrochloride Body mass index Biomarkers Platelet Aggregation Inhibitors medicine.drug |
| Zdroj: | Thrombosis Research. 134:552-557 |
| ISSN: | 0049-3848 |
| DOI: | 10.1016/j.thromres.2014.05.019 |
| Popis: | Introduction Patients treated with clopidogrel who have higher body size exhibit greater platelet reactivity than patients with lower body size. In a retrospective analysis of the FEATHER trial, we examined the relationship between platelet response to thienopyridines clopidogrel 75 mg (Clop-75), prasugrel 5 mg (Pras-5), and prasugrel 10 mg (Pras-10) using 3 body size indices: body weight (BW), body mass index (BMI), and body surface area (BSA). Relationships were assessed as continuous variables and as 4 incremental body size groups. Materials and Methods Aspirin-treated patients with stable coronary artery disease (N = 72) and a BW range of 45-134 kg received Clop-75, Pras-5, and Pras-10 in a 3-period, blinded, cross-over study. Platelet assays included maximum platelet aggregation (MPA) to 20 μM ADP by light transmission aggregometry, VerifyNow-P2Y12 reaction units (PRU), and vasodilator-associated stimulated phosphoprotein (VASP) phosphorylation platelet reactivity index (PRI). Exposure to active metabolites (AMs) was also assessed. Results Body size was a determinant of AM exposure and residual platelet reactivity regardless of type and dose of thienopyridine. BW and BSA demonstrated marginally stronger correlations with platelet reactivity; VASP-PRI demonstrated a stronger correlation with the body size than the other tests. Correlation coefficients ranged from a high of 0.64 (BW vs. PRI on Pras-5) to a low of 0.34 (BMI vs. MPA on Pras-10), but all were statistically significant (p Conclusions Using a comprehensive selection of body size indices, AM exposures, platelet function tests, and thienopyridine doses, we demonstrated a consistent inverse relationship between body size and response to clopidogrel and prasugrel. |
| Databáze: | OpenAIRE |
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