The clinical pharmacology of prazosin was studied in 10 hypertensive patients with chronic renal failure (group I) and in 9 hypertensive patients with normal renal function (group II). Prazosin, 2 mg, was given orally and blood samples were drawn at intervals for spectrofluorimetric assay. Blood pressure and heart rate were obtained at the same time. In the renal failure group, prazosin induced a significant decrease in systolic and diastolic blood pressures (-19 and -23%, respectively) at 90 min after intake, and these alterations were more rapid and marked than in the normal renal function group. Peak plasma concentration (Cmax) was higher (33.5 +/- 3.7 vs. 20.04 +/- 1.7 micrograms/liter, p < 0.01) and occurred earlier (1.3 +/- 0.2 vs. 2.7 +/- 0.3 hr, p < 0.005) in group I than in group II. The area under the plasma concentration-time curve (AUC0 infinity) was increased in the renal failure group (206.1 +/- 31.1 vs. 112.4 +/- 9.4 micrograms/hr/liter, p < 0.01). Apparent plasma elimination half-life (t 1/2) was not significantly different in the two groups (3.6 +/- 0.4 vs. 2.9 +/- 0.3 hr. ns). The mean blood pressure change (delta MBP%) was significantly correlated with the plasma level of prazosin in the renal failure group (n = 97, r = 0.489, p < 0.001) but not in patients with normal renal function (n = 74, r = 0.297, ns). The hypotensive action of prazosin is greater in patients with chronic renal failure, and the bioavailability or distribution of the drug is altered. Therefore, prazosin dosages should be modified in patients with impaired renal function.

Adult↗

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Acute and chronic effects of a new calcium inhibitor, nicardipine, on renal hemodynamics in hypertension.

Renal hemodynamics and natriuresis were studied in 10 hypertensive patients without renal failure, 2 and 4 h after oral intake of 30 mg nicardipine; then, nicardipine was given at a dose of 30 mg three times a day and the hemodynamic study was repeated on the 6th day (2 h after the morning dose). The first dose of nicardipine produced an increase in renal blood flow (from 888 +/- 45 to 999 +/- 59 ml/min 1.73 m2, p less than 0.01) and a decrease in renal vascular resistances (from 0.16 +/- 0.01 to 0.12 +/- 0.01 arbitrary unit, p less than 0.05). Glomerular filtration rate did not change and the decrease in filtration fraction was not significant. Sodium excretion increased markedly during the first 2 h (from 0.17 +/- 0.04 to 0.29 +/- 0.06 mmol/min, p less than 0.05). On the 6th day renal vascular resistances and filtration fraction remained lowered whereas glomerular filtration rate was unchanged. Nicardipine did not produce any significant alteration in plasma renin activity and plasma aldosterone after acute or chronic administration. These results confirm the potent renal vasodilatory effect of nicardipine; glomerular filtration rate was not significantly altered whereas renal blood flow and filtration fraction returned to normal levels. An early and transient natriuretic effect was observed after the first dose of nicardipine, and body weight showed a significant decrease during the study indicating that no sodium retention was induced by nicardipine.

Adult↗

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