Jasmine A Luzum1,2, Kevin M Sweet3, Philip F Binkley4, Tara J Schmidlen5, Joseph P Jarvis5, Michael F Christman5, Wolfgang Sadee6, Joseph P Kitzmiller6. 1. Center for Pharmacogenomics, Ohio State University College of Medicine, Columbus, Ohio, USA. jluzum@umich.edu. 2. Department of Clinical Pharmacy, University of Michigan College of Pharmacy, 428 Church St., Ann Arbor, Michigan, 48109, USA. jluzum@umich.edu. 3. Division of Human Genetics, Department of Internal Medicine, Ohio State University College of Medicine, Columbus, Ohio, USA. 4. Division of Cardiovascular Medicine and the Dorothy M. Davis Heart and Lung Research Institute, Ohio State University College of Medicine, Columbus, Ohio, USA. 5. Coriell Institute for Medical Research, Camden, New Jersey, USA. 6. Center for Pharmacogenomics, Ohio State University College of Medicine, Columbus, Ohio, USA.
Abstract
PURPOSE: This study examined whether a CYP2D6 polymorphism (CYP2D6*4) was related to beta-blocker maintenance dose in patients with heart failure. METHODS: Logistic regression modeling was utilized in a retrospective chart-review analysis of heart-failure patients (60% Male, 90% of European descent) to assess whether CYP2D6*4 (non-functional CYP2D6 allele present in 1 of 5 individuals of European descent) is associated with maintenance dose of carvedilol (n = 65) or metoprolol (n = 33). RESULTS: CYP2D6*4 was associated with lower maintenance dose of metoprolol (OR 0.13 [95% CI 0.02-0.75] p = 0.023), and a trend was observed between CYP2D6*4 and higher maintenance dose of carvedilol (OR 2.94 [95% CI 0.84-10.30] p = 0.093). None of the patients that carried CYP2D6*4 achieved the recommended target dose of metoprolol (200 mg/day). CONCLUSION: Consistent with the role of CYP2D6 in the metabolism of metoprolol, the tolerated maintenance dose of metoprolol was lower in CYP2D6*4 carriers compared to non-carriers. Consistent with the role of CYP2D6 in activation of carvedilol, tolerated maintenance dose of carvedilol was higher in CYP2D6*4 carriers compared to non-carriers. Further investigation is warranted to ascertain the potential of CYP2D6 as a potential predictive biomarker of beta-blocker maintenance dose in heart failure patients.
PURPOSE: This study examined whether a CYP2D6 polymorphism (CYP2D6*4) was related to beta-blocker maintenance dose in patients with heart failure. METHODS: Logistic regression modeling was utilized in a retrospective chart-review analysis of heart-failurepatients (60% Male, 90% of European descent) to assess whether CYP2D6*4 (non-functional CYP2D6 allele present in 1 of 5 individuals of European descent) is associated with maintenance dose of carvedilol (n = 65) or metoprolol (n = 33). RESULTS:CYP2D6*4 was associated with lower maintenance dose of metoprolol (OR 0.13 [95% CI 0.02-0.75] p = 0.023), and a trend was observed between CYP2D6*4 and higher maintenance dose of carvedilol (OR 2.94 [95% CI 0.84-10.30] p = 0.093). None of the patients that carried CYP2D6*4 achieved the recommended target dose of metoprolol (200 mg/day). CONCLUSION: Consistent with the role of CYP2D6 in the metabolism of metoprolol, the tolerated maintenance dose of metoprolol was lower in CYP2D6*4 carriers compared to non-carriers. Consistent with the role of CYP2D6 in activation of carvedilol, tolerated maintenance dose of carvedilol was higher in CYP2D6*4 carriers compared to non-carriers. Further investigation is warranted to ascertain the potential of CYP2D6 as a potential predictive biomarker of beta-blocker maintenance dose in heart failurepatients.
Authors: Henrike Wuttke; Thomas Rau; Roland Heide; Klaus Bergmann; Michael Böhm; Joachim Weil; Dierk Werner; Thomas Eschenhagen Journal: Clin Pharmacol Ther Date: 2002-10 Impact factor: 6.875
Authors: Steven G Terra; Daniel F Pauly; Craig R Lee; J Herbert Patterson; Kirkwood F Adams; Richard S Schofield; Bernadette S Belgado; Karen K Hamilton; Juan M Aranda; James A Hill; Hossein N Yarandi; Joseph R Walker; Michael S Phillips; Craig A Gelfand; Julie A Johnson Journal: Clin Pharmacol Ther Date: 2005-03 Impact factor: 6.875
Authors: Thomas Rau; Roland Heide; Klaus Bergmann; Henrike Wuttke; Ulrike Werner; Nico Feifel; Thomas Eschenhagen Journal: Pharmacogenetics Date: 2002-08
Authors: Thomas Giessmann; Christiane Modess; Ute Hecker; Michael Zschiesche; Peter Dazert; Christiane Kunert-Keil; Rolf Warzok; Georg Engel; Werner Weitschies; Ingolf Cascorbi; Heyo K Kroemer; Werner Siegmund Journal: Clin Pharmacol Ther Date: 2004-03 Impact factor: 6.875
Authors: T Rau; H Wuttke; L M Michels; U Werner; K Bergmann; M Kreft; M F Fromm; T Eschenhagen Journal: Clin Pharmacol Ther Date: 2008-11-26 Impact factor: 6.875
Authors: Nasir Ali Afsar; Henrike Bruckmueller; Anneke Nina Werk; Muhammad Kashif Nisar; H R Ahmad; Ingolf Cascorbi Journal: Sci Rep Date: 2019-05-13 Impact factor: 4.379