[Nifedipine-clonidine combination in essential hypertension. Hemodynamic and neurohumoral findings of the combination in comparison with the effect of the individual substances]. / Nifedipin-Clonidin-Kombination bei essentieller Hypertonie. Hämodynamische und neurohumorale Befunde der Kombination im Vergleich zur Wirkung der Einzelsubstanzen.

In 10 patients with moderate essential hypertension, the neurohumoral and hemodynamic effects of 4 days' treatment with 2 x 75 micrograms clonidine (C), 2 x 20 mg nifedipine retard (N), and a combination of the two (C/N) were studied and compared with baseline values. The heart rate decreased significantly from a mean of 79 to 67 bpm (p less than 0.05) under C, increased again to 73 bpm (p greater than 0.05) under N, and decreased once more to 68 bpm (p less than 0.05) under C/N. The systolic blood pressure decreased from a mean of 184 to 171 under C, 168 after N, and 161 (p less than 0.01) under C/N; significant decreases of diastolic blood pressure were also observed (from 113 to 104 under C, 107 under N, 100 mmHg under C/N (p less than 0.05). Norepinephrine decreased from 440 to 281 under C (p less than 0.01), increased to 391 (p greater than 0.05) after N, and measured 404 pg/ml (p less than 0.05) under C/N. PRA decreased significantly under C, increased under N, and remained unchanged under C/N. These findings demonstrate that combined treatment with lowdose nifedipine and clonidine leads to an additive reduction of blood pressure. The disadvantage of neurohumoral counterregulation of nifedipine are neutralized by clonidine.

Interactions of clonidine and nifedipine in moderately severe hypertensive patients.

In ten patients (age: 47-59 yr) with moderately severe essential hypertension, the humoral and hemodynamic effects of a 4-day therapy with 2 x 75 micrograms clonidine, 2 x 20 mg nifedipine (slow-release), and their combination were investigated and compared with baseline values. The following measurements were observed under clonidine (C), nifedipine (N), and on combination (C/N), respectively: heart rate fell significantly under C from a mean of 79 to 67/min (P less than .05), increased to 73/min after N (P greater than .05) and fell again to 68/min under combination (P less than .05). Systolic blood pressure (Riva-Rocci method) decreased from a mean of 184 to 171 (C), 168 (N) and 161 mm Hg (C/N), respectively (P less than .01). Diastolic blood pressure was also significantly altered (113 vs. 104 (C), 107 (N), and 100 mm Hg (C/N); P less than .05). Stroke volume (ECHO) was not altered significantly (77 vs. 71 (C), 79 (N), and 80 mL (C/N), respectively), whereas cardiac output dropped from 5.9 to 4.9 L/min (C; P less than .05), increased to 5.7 (N; P greater than .05), and dropped again to 5.3 L/min (C/N; P greater than .05). Peripheral vascular resistance increased from a mean of 2091 to 2297 (C), fell to 1933 (N), and increased again to 2138 dyn/sec/cm-5 (C/N). Plasma norepinephrine levels fell from 440 to 281 (C; P less than .01), increased to 391 (N; P greater than .05), and fell again to 404 pg/mL (C/N; P greater than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of clonidine and nifedipine on left ventricular hypertrophy and muscle mass in hypertensive patients.

In a parallel group randomized trial we compared the echocardiographically documented effects of clonidine (cl) versus nifedipine (nf) on left ventricular hypertrophy (LVH) and muscle mass (LVM) in hypertensive subjects. Twenty-one patients with concentric LVH (thickness of interventricular septum, IVS, and left posterior wall, LPW, above 11 mm) were given a 2D and M-mode echocardiogram before (pre) and 12 and 24 weeks, respectively, after therapy was initiated (mean oral cl dosage 150 micrograms; nf, 30 mg/day). At the end of the follow-up period in the cl group blood pressure declined by an average of 16/11 mm Hg compared with 30/20 mm Hg in the nf group (intergroup differences, NS). The thickness of the IVS decreased from a mean of 15.0 +/- 1.9 mm and 15.1 +/- 1.5 pre-therapy to 12.6 +/- 2.3 for cl (p = 0.0001) and 13.1 +/- 1.5 mm for nf (p = 0.001) after 24 weeks, respectively. This was similar to the regression of the LV posterior wall with 14.7 +/- 1.5 and 14.5 +/- 1.6 mm pre-therapy to 12.0 +/- 1.1 in the cl group (p = 0.0001) and 12.7 +/- 1.7 for nf (p = 0.006). As the internal LV-diameter were relatively constant over the treatment period, the calculated values for LVM dropped from a mean of 406.5 +/- 125.9 and 401.4 +/- 106.6 to 274.8 +/- 78.7 and 297.5 +/- 85.0 g, respectively, corresponding to -31.6 +/- 11.0% for cl (p = 0.0001) and -25.2 +/- 12.6% for nf (p = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

The pharmacokinetic profile of pyrazinobutazone in man.

The rate of absorption of phenylbutazone from pyrazinobutazone (Ranoroc/Carudol) capsules is distinctly lower than that from phenylbutazone capsules. The capsules are bioequivalent to an equimolar dose of Na-phenylbutazone in solution, as judged by both the area under the plasma level curves (AUC), and the sum of the unchanged phenylbutazone excreted in the urine. A single dose of 300 mg pyrazinobutazone produces maximum plasma levels of 35.2 +/- 1.1 micrograms/ml at 5.5 h after administration (+/- SEM, 70 kg bodyweight, N = 39). Two dosage schedules for long-term therapy were tested (2400 and 1500 mg/week). Both produced accumulation to saturation plasma levels within approximately three days. The concentration of phenylbutazone obtained with the lower dosage was about 110 micrograms/ml plasma. This corresponds with the recommendations for long-term therapy with phenylbutazone. With the higher dosage, the plasma levels were elevated by only 25%, however, the renal elimination of unchanged drug and the number of side-effects were remarkably increased. The recommended dosage scheme is specifically adapted to the pharmacokinetics of pyrazinobutazone.