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dc.contributor.authorChong, C.en
dc.contributor.authorDrury, N.en
dc.contributor.authorLicari, G.en
dc.contributor.authorFrenneaux, M.en
dc.contributor.authorHorowitz, J.en
dc.contributor.authorPagano, D.en
dc.contributor.authorSallustio, B.en
dc.identifier.citationEuropean Journal of Clinical Pharmacology, 2015; 71(12):1485-1491en
dc.description.abstractPurpose: Perhexiline is a prophylactic anti-ischaemic agent with weak calcium antagonist effect which has been increasingly utilised in the management of refractory angina. The metabolic clearance of perhexiline is modulated by CYP2D6 metaboliser status and stereoselectivity. The current study sought to (1) determine whether the acute accumulation of perhexiline in the myocardium is stereoselective and (2) investigate the relationship between duration of short-term therapy and the potential stereoselective effects of perhexiline within myocardium. Method: Patients (n  = 129) from the active arm of a randomised controlled trial of preoperative perhexiline in cardiac surgery were treated with oral perhexiline for a median of 9 days. Correlates of atrial and ventricular concentrations of enantiomers were sought via univariate followed by multivariate analyses. Results: Myocardial uptake of both (+) and (−) perhexiline was greater in ventricles than in atria, and there was more rapid clearance of (−) than (+) perhexiline. The main determinants of atrial uptake of both (+) and (−) perhexiline were the plasma concentrations [(+) perhexiline: β = −0.256, p = 0.015; (−) perhexiline: β = −0.347, p = 0.001] and patients’ age [(+) perhexiline: β = 0.300, p = 0.004; (−) perhexiline: β = 0.288, p = 0.005]. Atrial uptake of (+) enantiomer also varied directly with duration of therapy (β = 0.228, p = 0.025), while atrial uptake of (−) perhexiline varied inversely with simultaneous heart rate (β = −0.240, p = 0.015).en
dc.description.statementofresponsibilityCher-Rin Chong, Nigel E. Drury, Giovanni Licari, Michael P. Frenneaux, John D. Horowitz, Domenico Pagano, Benedetta C. Sallustioen
dc.rights© Springer-Verlag Berlin Heidelberg 2015en
dc.subjectPerhexiline; metabolism; pharmacokinetics; drug uptake; stereoselectivityen
dc.titleStereoselective handling of perhexiline: implications regarding accumulation within the human myocardiumen
dc.typeJournal articleen
pubs.library.collectionMedicine publicationsen
dc.identifier.orcidChong, C. [0000-0001-8722-8937]en
dc.identifier.orcidLicari, G. [0000-0002-4056-0681]en
dc.identifier.orcidHorowitz, J. [0000-0001-6883-0703]en
dc.identifier.orcidSallustio, B. [0000-0002-0186-3073]en
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