PMID: identifiant
de la référence Pubmed : |
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 (22472992) |
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| titre : |
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Pharmacokinetic and pharmacodynamic variability of fluindione in octogenarians. |
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| auteur(s) : |
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Emmanuelle Comets ( ) 1, Bertrand Diquet2, Sylvie Legrain3, Marie-Geneviève Huisse4, Alban Godon5, Corinne Bruhat6, Marie-Paule Chauveheid7, Sandrine Delpierre3, Xavier Duval1, 8, Gilles Berrut9, Céline Verstuyft10, 11, Marie-Claude Aumont12, France Mentré1 |
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| laboratoire : |
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| résumé : |
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In the PREPA observational study, we investigated the factors influencing pharmacokinetic and pharmacodynamic variability in the responses to fluindione, an oral anticoagulant drug, in a general population of octogenarian inpatients.Measurements of fluindione concentrations and international normalized ratio (INR ) were obtained for 131 inpatients in whom fluindione treatment was initiated. Treatment was adjusted according to routine clinical practice. The data were analyzed using nonlinear mixed-effects modeling, and the parameters were estimated using MONOLI X 3.2. The pharmacokinetics (PK) of fluindione was monocompartmental, whereas the evolution of INR was modeled in accordance with a turnover model (inhibition of vitamin K recycling). Interindividual variability (II V) was very large. Clearance decreased with age and with prior administration of cordarone. Patients who had undergone surgery before the study had lower IC50 values, leading to an increased sensitivity to fluindione. Pharmacokinetic exposure is substantially increased in elderly patients, warranting a lower dose of fluindione. |
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| domaine : |
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langue du texte
intégral : |
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Anglais |
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| ISSN : |
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0009-9236 |
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| type de publication : |
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Articles dans des revues avec comité de lecture |
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| DOI : |
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10.1038/clpt.2011.309 |
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| journal : |
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| Clinical Pharmacology and Therapeutics (Clin Pharmacol Ther) |
| Publisher |
American Society for Clinical Pharmacology and Therapeutics |
| ISSN |
0009-9236 (eISSN : 1532-6535) |
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| Audience : |
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internationale |
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| date de publication : |
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05/2012 |
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| volume : |
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91 |
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| numéro : |
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5 |
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| page, identifiant, ... : |
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777-86 |
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| mots-clés auteur : |
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fluindione – antivitamin K – oral anticoagulant – elderly – pharmacokinetics – pharmacodynamics – International Normalised Ratio (INR) |
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| Descripteur(s) MeSH : |
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Aged – Aged – 80 and over – Anticoagulants – Female – Humans – International Normalized Ratio – Male – Phenindione |
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| contrat, financement : |
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This study was supported by a grant from the Groupement d'Intérêt Scientifique (GIS) Longévité, and the genotyping analyses were financed by a grant from the Comité d'Orientation Stratégique et de Suivi des Essais Cliniques (COSSEC, INSERM, Paris, France). The promoter of the study was the Institut de la Santé et de la Recherche Médicale (INSERM, Paris, France). |
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