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  • 1985-1989  (2)
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 29 (1985), S. 401-403 
    ISSN: 1432-1041
    Keywords: endralazine ; hypertension ; once daily dosing ; atenolol ; propranolol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We report the first placebo controlled parallel group study of once daily endralazine (5–20 mg) in hypertension uncontrolled by a beta-blocker plus a diuretic. Following a 4-week run-in period 22 patients with a sitting mean arterial pressure (MAP) greater than 110 mm Hg were entered into the study and received either endralazine 5 mg or placebo. Blood pressure was measured 2 h and 24 h after dosing and the drug dose doubled at 2 and 4 weeks if the 24-h MAP remained 〉110 mg Hg. The final blood pressure assessment was made after 6 weeks treatment in the 19 patients who completed the study. Three patients withdrew from the study because of side effects. The hypotensive effect (sitting) was in excess of placebo at 2 h by 15.8 mm Hg systolic (NS), 15.4 mm Hg diastolic (p〈0.01), 15.5 mm Hg MAP (p〈0.02) and at 24 hours by 7.7 mm Hg systolic (NS), 8.9 mm Hg diastolic (p〈0.02) and 11.1 mm Hg MAP (p〈0.02). This study suggests that endralazine should be prescribed twice daily.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 28 (1985), S. 85-88 
    ISSN: 1432-1041
    Keywords: debrisoquine oxidation ; metoprolol metabolism ; oxidation phenotype ; β-blockade ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary After a single 200 mg oral dose of metoprolol tartrate the mean metoprolol AUC was found to be six-fold higher in poor metabolizers (PMs) of debrisoquine than in extensive metabolizers (EMs). This was associated with impaired metabolic clearance via α-hydroxylation and O-dealkylation. A population study (n=143) has shown a bimodal distribution in the ratio of metoprolol: α-hydroxymetoprolol recovered in urine which was correlated highly with the debrisoquine metabolic ratio. Nine per cent of the population were PMs. Plasma metoprolol concentrations three hours after a 100 mg oral dose of metoprolol were greater than 200 ng/ml in PMs but were lower than this in most EMs. This dose of metoprolol given once daily provided a clinically significant reduction (16%) in exercise heart rate in PMs after 24 hours. EMs require conventional doses (100 mg b.d.) to achieve the same degree of β-blockade. Preliminary data from family studies support the view that the defect in metoprolol oxidation is inherited. In 12 hypertensive patients who were EMs we compared the β-blocking activity and antihypertensive effect of chronic treatment with metoprolol 200 mg once daily (conventional and long-acting formulations), with those of atenolol 100 mg once daily and placebo. The effects of all active preparations were similar at 3.5 hours but atenolol was superior to all metoprolol formulations at 24 hours after dosing. It is concluded that for the majority of patients metoprolol should be prescribed twice daily when using currently available dosage forms. Relationships between oxidation phenotype and side-effects should be examined.
    Type of Medium: Electronic Resource
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