Different effects of nifedipine and amlodipine on circulating catecholamine levels in essential hypertensive patients (vol 16, pg 1357, 1998)

Objective To compare the acute and chronic effects of nifedipine retard (NP A), nifedipine gastrointestinal therapeutic system (NGITS) and amlodipine a t trough and peak plasma concentrations of drug on blood pressure and heart rate, and on plasma norepinephrine and epinephrine levels in patients with mild-to-moderate hypertension (diastolic blood pressure 95-115 mmHg). Design and methods After 3-4 weeks' placebo treatment, patients of both sex es were randomly allocated to be administered 10 or 20 mg NPA twice a day, 30 or 60 mg NGITS once a day, and 5 or 10 mg amlodipine once a day for 6 we eks. Initially, for the first 2 weeks, the lowest dose of each drug was use d, but higher doses were administered after 2 weeks if sitting diastolic bl ood pressure was > 90 mmHg, Patients were evaluated after administration of the first dose and after 6 weeks' therapy in a hospital setting. Blood sam ples were taken for high-performance liquid chromatography measurement of c atecholamine and drug levels at various intervals for a period covering tro ugh to peak drug level ranges. Results Administration of all three drugs reduced clinic blood pressure to the same level after 6 weeks' therapy, but heart rate was increased slightl y only with amlodipine (P< 0.05), Administration of NPA reduced blood press ure more abruptly whereas administrations of NGITS and amlodipine induced s moother falls after acute and chronic treatments: a significant increase in heart rate was observed with amlodipine after chronic treatment. Both acut e and chronic treatments with NPA (n =19) increased norepinephrine levels ( P < 0.01) transiently (2-4 h). In contrast, administration of NGITS (n = 22 ) did not increase norepinephrine levels and even induced a slight but sign ificant decrease in norepinephrine levels 5-6 h after chronic treatments. A lthough administration of amlodipine (n = 22) did not increase norepinephri ne levels transiently either after acute or after chronic administration, i t did induce a sustained rise in basal norepinephrine levels by more than 5 0% after chronic therapy (P < 0.01). Plasma epinephrine levels were not inc reased by any of the treatments and even a slight decrease was observed 4 h after administration of a dose following chronic treatments with NGITS and amlodipine (P < 0.05). Conclusions The transient increase in norepinephrine levels observed with N PA and the sustained increases in norepinephrine levels observed after chro nic treatment with amlodipine suggest that sympathetic activation occurs wi th those two drugs. The lack of increase in norepinephrine levels after adm inistration of NGITS suggests that this formulation does not activate the s ympathetic system. The lowering of epinephrine levels after administrations of NGITS and amlodipine suggests that inhibition of release of epinephrine by the adrenal medulla occurs with longer-acting dihydropyridine formulati ons, J Hypertens 16:1357-1369 (C) 1998 Lippincott Williams & Wilkins.