Olivier Steichen

Effects of rabeprazole on the antiplatelet effects and pharmacokinetics of clopidogrel in healthy volunteers

BACKGROUNDnSeveral studies have suggested that proton-pump inhibitors (PPIs), mostly omeprazole, interact with clopidogrel efficacy by inhibiting the formation of its active metabolite via CYP2C19 inhibition. Whether this occurs with all PPIs is a matter of debate. As rabeprazole is a less potent CYP2C19 inhibitor than other PPIs, we studied the interaction between rabeprazole and the antiplatelet actions and pharmacokinetics of clopidogrel.nnnAIMnTo demonstrate the non-inferiority of rabeprazole over placebo using change in platelet reactivity index (PRI; vasodilator-stimulated phosphoprotein [VASP] assay) in a predefined population of good clopidogrel responders. Omeprazole was used as the positive control.nnnMETHODSnIn this randomized three-period crossover study in healthy volunteers, 36 healthy men received clopidogrel (75 mg/day for 7 days) with placebo, omeprazole (20mg/day) or rabeprazole (20mg/day). Clopidogrel antiplatelet effects and disposition kinetics were assessed on day 7 of combination therapy. Non-inferiority threshold was predefined as an upper limit of the 90% confidence interval for the difference in change in PRI between placebo and rabeprazole of<10% in good clopidogrel responders.nnnRESULTSnIn good clopidogrel responders (inhibition of VASP index>30%), the clopidogrel antiplatelet effect remained non-inferior to placebo during rabeprazole (difference 3.4% [-1.7; 8.5]) but not omeprazole (difference 7.5% [2.5; 12.6]) co-administration. The AUC0-24 and Cmax of active clopidogrel metabolite decreased with both omeprazole and rabeprazole, and conditions of bioequivalence were not met, except for AUC0-24 with rabeprazole.nnnCONCLUSIONSnRabeprazole does not interact with clopidogrel to the same extent as omeprazole. However, under our experimental conditions and proton-pump inhibitor doses, there was no significant pharmacodynamic interaction between rabeprazole or omeprazole and clopidogrel, despite a significant decrease in the formation of clopidogrel active metabolite.

Building an Ontology of Hypertension Management

The analysis of customized decisions during hypertension management in a specialized unit requires a detailed representation of clinical cases. We are building a specific ontology to code medical records and process them with computerized tools. Relevant concepts to describe and justify medical decisions are extracted from three sources: (i) Clinical guidelines; (ii) Items of the semi-structured medical record form used in the clinical unit; (iii) Free-text answers from 5,000 completed record forms. Combining terminological sources is mandatory to cover the whole spectrum of possible justifications for clinical decisions, including contextual specificities and patients particulars.

Utiliser et construire des ontologies en médecine : le primat de la terminologie

RESUME. Le Web semantique reclame par definition de construire des ontologies permettant, par leur caractere formel, d’automatiser un certain nombre de tâches liees principalement a la recherche d’information et a la classification. Dans cet article, nous montrons que la medecine a des specificites qui contraignent l’usage des ontologies et leur construction. Ces specificites amenent a prendre en compte le caractere linguistique des thesaurus medicaux et a les utiliser en coordination avec les ontologies pour exploiter les informations medicales. En complement, la construction des ontologies peut prendre en compte l’expression linguistique des connaissances en utilisant les textes generes par les professionnels de sante durant leur activite. Nous donnons des exemples avec des applications dans trois specialites medicales differentes.