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However, it is still unknown how much of the 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 area under the curve (AUC) varied 4.7\u2010fold and torsemide AUC 3.5\u2010fold. 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, \u20102C9, and OATP1B1 explained only 39%, 2%, and 39% of that variation, respectively. Comparable results for genetically explained variation in pharmacokinetics and pharmacodynamics have been found for other substrates of these enzymes earlier. 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