Heritability of metoprolol and torsemide pharmacokinetics

Johannes Matthaei, Jürgen Brockmöller, Mladen Tzvetkov, Daniel Sehrt, Cordula Sachse-Seeboth, Jacob v. B. Hjelmborg, Sören Möller, Ulrich Halekoh, Ute Hofmann, Matthias Schwab, Reinhold Kerb

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Genetic variation in the pharmacokinetics of metoprolol and torsemide due to polymorphisms in CYP2D6, CYP2C9 and OATP1B1 has been extensively studied. However, it is still unknown how much of variation in pharmacokinetics of these two clinically important drugs in total is due to genetic factors. Metoprolol and torsemide were intravenously administered to 44 monozygotic and 14 dizygotic twin pairs. Metoprolol AUC varied 4.7-fold and torsemide AUC 3.5-fold. A very high fraction of AUC variations, 91% of metoprolol and 86% of torsemide, were found to be due to additive genetic effects. However, known genetic variants of CYP2D6, -2C9 and OATP1B1 explained only 39%, 2% and 39% of that variation. Comparable results for genetically explained variation in pharmacokinetics and pharmacodynamics have been found for other substrates of these enzymes earlier. These findings indicate that a substantial fraction of the heritable variability in the pharmacokinetics of metoprolol and torsemide remains to be elucidated. This article is protected by copyright. All rights reserved.
TidsskriftClinical Pharmacology and Therapeutics
Udgave nummer6
Sider (fra-til)611-21
StatusUdgivet - dec. 2015



Matthaei, J., Brockmöller, J., Tzvetkov, M., Sehrt, D., Sachse-Seeboth, C., Hjelmborg, J. V. B., Möller, S., Halekoh, U., Hofmann, U., Schwab, M., & Kerb, R. (2015). Heritability of metoprolol and torsemide pharmacokinetics. Clinical Pharmacology and Therapeutics, 98(6), 611-21. https://doi.org/10.1002/cpt.258