PubMed · 15749801
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M M Massin, C Coremans. 2005. Recurrent syncope.. https://doi.org/10.1136/pgmj.2004.022145
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We investigated the stereoselective kinetic disposition and metabolism of metoprolol (MET) in rats. The racemic MET (15 mg/kg) was given by oral gavage and blood samples were collected from 0 to 10h (n=6 at each time point). The enantiomeric concentrations of MET and its metabolites alpha-hydroxymetoprolol (alpha-OHM) and O-demethylmetoprolol (ODM) were determined by HPLC using a Chiralpak AD chiral column and fluorescence detection. The pharmacokinetic parameters of unchanged MET and the formation of ODM did not show to be stereoselective. In contrast, the AUC (ng h/mL) of alpha-hydroxymetoprolol isomers were higher to I'R [638.2(525.2-706.2) for 1'R2R and 659.6(580.4-698.1) for 1'R,2S, mean, (95%CI)] than to I'S products [58.3(47.4-66.1) for 1'S,2R and 57.1(44.7-67.9) for 1'S,2S, mean, (95%CI)]. We conclude that the kinetic disposition of unchanged MET and the formation of ODM are not enantioselective in rats but the metabolism of alpha-OHM yields predominantly the 1'R-product.
BACKGROUND: The treatment of heart failure (HF) due to left ventricular systolic dysfunction has been defined in recent guidelines, but these guidelines are not always applied in routine clinical practice. One of the objectives of the ETICS study was to evaluate medical treatment at discharge and after 1 year in patients hospitalised for a first episode of congestive HF due to left ventricular systolic dysfunction in 2000. METHODS: One hundred and seventy nine patients (63% males, mean age of 69+/-13 years) with an ejection fraction < or = 40% were prospectively included. The main aetiology was ischaemic heart disease (44%). RESULTS: The drugs prescribed at discharge and at one year, respectively, were loop diuretics in 95% and 91% of cases, angiotensin-converting enzyme (ACE) inhibitors in 82% and 75%, spironolactone in 35% and 37%, beta-blockers in 25% and 41%, digitalis glycosides in 34% and 30% of cases, and nitrates in 20% and 16% of cases. ACE inhibitors were prescribed at discharge and at 1 year at dosages reaching 64+/-29% and 72+/-30% of the recommended doses, respectively, and beta-blockers were prescribed at 26+/-16% and 35+/-25% of recommended doses, respectively. CONCLUSION: Diuretics and ACE inhibitors are largely prescribed in HF due to left ventricular systolic dysfunction, followed by spironolactone. Beta-blockers are still underused both in terms of the rate of patients receiving them and the daily doses. These results highlight the value of continuing to widely circulate official practice guidelines in order to improve the management of HF due to left ventricular systolic dysfunction.