Disease relevance of H119-66

• Metoprolol and alpha-hydroxymetoprolol concentrations and reduction in essential tremor [1].
• Patients with chronic renal failure presented plasma accumulation of the 4 alpha-hydroxymetoprolol isomers and of both metoprolol acidic metabolite enantiomers [2].

High impact information on H119-66

• There was a significant inverse relationship between physiologic urinary pH and sequential dextromethorphan: dextrorphan MRs as well as metoprolol: alpha-hydroxymetoprolol MRs in men and women, with metabolic ratios varying up to six-fold with metoprolol and up to 20-fold with dextromethorphan (ANCOVA P < 0.001) [3].
• A reduction of glomerular filtration rate (GFR) by 70 to 80% increased the elimination half-life of total metabolites and of the active metabolite alpha-hydroxymetoprolol about 3-fold [4].
• The log10 metoprolol/alpha-hydroxymetoprolol ratio correlated positively with the AUC of desipramine (P < .01) and with the AUC ratio of desipramine/imipramine (P < .05) but negatively with the AUC ratio of 2-hydroxyimipramine/imipramine (P < .05) [5].
• Microsomes from one liver formed no detectable alpha-hydroxymetoprolol, and O-demethylation by these microsomes corresponded to the low affinity site observed in eight other livers [6].
• The formation kinetics of O-demethylmetoprolol and alpha-hydroxymetoprolol were characterized in five different lots of the cDNA-expressed P4502D6 [7].

Biological context of H119-66

• The purpose of this study was to examine the influence of input rate on the stereoselective and nonstereoselective pharmacokinetics of metoprolol, alpha-hydroxymetoprolol, and its acid metabolite [8].
• There were no significant differences between the groups in the frequency of slow acetylator and poor oxidiser phenotypes, or in the frequency distribution profiles of acetylation (monoacetyldapsone/dapsone) and oxidative metabolic ratio (log metoprolol/alpha-hydroxymetoprolol) [9].

Anatomical context of H119-66

• High-performance liquid chromatographic determination of metoprolol and alpha-hydroxymetoprolol concentrations in human serum, urine, and cerebrospinal fluid [10].

Associations of H119-66 with other chemical compounds

• The methods were employed to determine the concentrations of alpha-hydroxymetoprolol stereoisomers in a metabolism study of multiple-dose administration of racemic metoprolol to hypertensive patients phenotyped as extensive metabolizers of debrisoquine [11].

Gene context of H119-66

• A continuous infusion of metoprolol (3 mg.min-1 i.v) was started and serial blood samples for plasma catecholamines, NPY as well as metoprolol and its major metabolite alpha-hydroxymetoprolol were obtained from the contralateral arm [12].

Analytical, diagnostic and therapeutic context of H119-66

• Determination of metoprolol and alpha-hydroxymetoprolol in plasma by high-performance liquid chromatography [13].
• The concentrations of alpha-hydroxymetoprolol, the major metabolite in plasma, were similar after jejunal and colonic perfusion, but higher than those observed after intravenous administration [14].
• Direct stereoselective separation on chiral stationary phase was developed for HPLC analysis of the four stereoisomers of alpha-hydroxymetoprolol in human plasma and urine [11].

References