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  • 1
    ISSN: 1432-1041
    Keywords: felodipine ; metoprolol ; atenolol ; hypertension ; exercise ; pharmacokinetics ; adverse effects ; hypotensive action
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A study has been performed in thirteen patients with essential hypertension, WHO Class I–II, and a diastolic blood pressure ≥95 mm Hg, on beta-blocker (metoprolol or atenolol) monotherapy, who were also given felodipine 10 mg b.d. for 28 days. The acute and steady state blood pressure response at rest and during exercise, and the pharmacokinetics of felodipine and metoprolol, were examined. Felodipine in combination with the beta-blocker reduced the systolic and diastolic blood pressures acutely and at steady-state. The duration of the effect was longer at steady-state. There was a significant correlation between the plasma concentration of felodipine and the change in blood pressure. The increase in systolic blood pressure during exercise was of the same magnitude before and after felodipine administration. No change in resting supine heart rate was found after the administration of felodipine. There were no significant differences in the pharmacokinetics of felodipine during long-term treatment, except for the trough plasma concentration, which was increased at steady-state, even though cumulation of felodipine and its metabolite did not occur. There was a significant decrease in the maximal plasma concentration and AUC of metoprolol after 28 days of treatment with felodipine, but its elimination half-life was not changed. The adverse reactions reported during this study were those generally seen after dihydropyridines and, except for two patients who were withdrawn after the first study day, the effects were well tolerated.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-7241
    Keywords: felodipine ; hypertension ; impaired renal function
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Twenty-three patients with severe hypertension and impaired renal function were included in an open study of the efficacy and tolerance of felodipine treatment over 6 months. All patients were previously treated with a diuretic, a beta blocker, and a vasodilator, and eight of them also received an ACE inhibitor. At the start of felodipine treatment the previously used vasodilator was withdawn. In nine patients the concomitant antihypertensive treatment was reduced during the study. The glomerular filtration rate (GFR), as51Cr EDTA clearance, was determined before and at the end of the study. The blood pressure (BP) and heart rate (HR) were recorded at all clinical visits in the moring 12 hours after the evening dose of felodipine and 2 hours after the morning dose. Plasma concentrations of felodipine were measured at every visit before the morning dose and 2 hours after dose. The BP was reduced after felodipine was substituted for the previously used vasodilator. A significant additional antihypertensive effect was recorded 2 hours after the dose and amounted to −37±22/−15±12 mmHg (p=0.0001/p=0.0002) at 6 months. The effect measured 12 hours after the dose was less pronounced and was −11±28/−6±10 mmHg (p=0.15/p=0.03). Mean GFR was unchanged during the study, 38±19 versus 38±19 ml/min (n=16). There was a sixfold interindividual variation in the trough plasma concentrations at steady state at the same drug dosage. Higher plasma concentrations seemed to be required to achieve the same antihypertensive effects as in patients with less severe hypertension and normal renal function. The frequency of adverse effects and the number of patients withdrawn (n=5) were somewhat higher than reported in patients with normal renal function and may be related to the high doses (up to 80 mg daily) used. In conclusion our data suggest that felodipine, in addition to other antihypertensives, is effective and is usually well tolerated in the treatment of patients with severe hypertension and reduced renal function. In order to ensure a more even reduction of BP over the day, a tid dosage regimen of the plain-tablet formulation used in this study may be preferable.
    Type of Medium: Electronic Resource
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