Felodipine in the treatment of patients with severe hypertension and impaired renal function

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 The frequency of adverse effects and the number of patients withdrawn (n=5) were somewhat higher than reported in patients with normal renal function and may be related to the high doses (up to 80 mg daily) used.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.