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- W2000967958 abstract "The hypothesis that variability in metoprolol metabolism stereoselectivity is related to debrisoquin oxidation phenotype was tested in six extensive (EM) and six poor (PM) debrisoquin metabolizers. In EM, plasma AUCs for (S)-metoprolol were 35% higher than for (R)-metoprolol, whereas in PM, AUCs for (S)-metoprolol were lower than for (R)-metoprolol. AUCs for total metoprolol correlated with the ratio of (S)- to (R)-metoprolol AUC. The renal clearance of metoprolol was also stereoselective but to the same extent in both EM and PM. Findings suggest that the enzyme system responsible for polymorphic oxidation of the debrisoquin-type is stereoselective. The relation between log total metoprolol plasma concentration and response (β-blockade) was shifted to the right in PM relative to EM, which is compatible with a difference in pharmacologic activity of metoprolol enantiomers. Kinetic predictions based on total drug measurements will tend to overestimate dynamic differences between EM and PM, but the magnitude of the error is relatively small, and, in absolute terms, there is a large difference in pharmacologic activity between the phenotypes (β-blockade at 24 hr: EM = 5.3 ± 5.6%; PM = 18.9 ± 3.8%). Clinical Pharmacology and Therapeutics (1983) 34, 732–737; doi:10.1038/clpt.1983.242" @default.
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- W2000967958 date "1983-12-01" @default.
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- W2000967958 title "Differential stereoselective metabolism of metoprolol in extensive and poor debrisoquin metabolizers" @default.
- W2000967958 doi "https://doi.org/10.1038/clpt.1983.242" @default.
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