Acute effect of labetalol on hypertensive brachial artery.

Forearm arterial hemodynamics, including measurements of brachial artery diameter and compliance with pulsed Doppler velocimetry, were determined before and after acute administration of labetalol in patients with sustained essential hypertension. Labetalol caused a significant and rapid drop in blood pressure, with a decrease in forearm vascular resistance and an increase in brachial blood flow. Brachial artery diameter did not change, whereas arterial compliance increased significantly. The study provided evidence that labetalol caused a shift of the pressure-brachial artery diameter curve toward lower values of blood pressure, indicating a pharmacological effect of alpha and beta blockade on the hypertensive arterial wall.

[Hemodynamic effects of labetalol on the humeral artery of the hypertensive patient. A double-blind study versus placebo]. / Effets hémodynamiques du labétalol sur l'artère humérale du sujet hypertendu. Etude en double-aveugle contre placebo.

Forearm arterial hemodynamics, including measurements of brachial artery diameter and compliance with pulsed Doppler velocimetry were determined before and after acute administration of labetalol in patients with sustained essential hypertension. Labetalol caused a significant and rapid drop in blood pressure with a decrease in forearm vascular resistance and an increase in brachial blood flow. Brachial artery diameter did not change while arterial compliance significantly increased. The study provided evidence that labetalol caused a shift of the pressure-brachial artery diameter curve toward lower values of blood pressure, indicating a pharmacological effect of alpha and beta blockade on the hypertensive arterial wall.

Guanfacine kinetics in patients with hypertension.

Guanfacine kinetics were studied in 19 patients with hypertension after single and repeated oral doses. The single-dose study was performed in two homogeneous groups who received 2 mg (n = 9) and 4 mg (n = 10). The plasma concentrations were fitted in a two-compartment open model with first-order absorption. After a lag time of 0.8 hr, the absorption occurred rapidly (t 1/2 congruent to 0.53 hr). The fast and slow elimination phases occurred with t 1/2s of 2 and 19 hr. At therapeutic levels the percent of drug in red blood cells (55%) was independent of total drug concentration. Peak plasma levels had small interindividual variations. Comparison of kinetic parameters and AUC at the two doses studied demonstrated that their bioavailability was equal and the kinetics were linear. In a multiple-dosing study, performed in the same subjects, the plasma levels at steady state were in good agreement with the predicted values (p less than 0.001) and proportional to daily dosage. A single method based on four blood samples collected after 24, 28, 32, and 36 hr allows a reasonable prediction of the effective steady-state plasma levels during chronic dosing with guanfacine.

Pindolol availability in hypertensive patients with normal and impaired renal function.

Intravenous and oral pharmacokinetics of pinlolol were studied in 18 hypertensive patients-9 with normal renal function and 9 with impaired renal function. Analysis of data showed that a linear two-compartment model was suitable to describe the pindolol kinetics. Compared with patients with normal renal function, patients with chronic renal failure exhibited: (1) unchanged transfer rate constants and distribution volumes and (2) decreased total body clearance with decreased renal clearance and unchanged nonrenal clearance. Analysis of oral data by the Loo-Riegelman method showed that the pindolol absorption kinetic was not first order. Compared with patients with normal renal function, patients with chronic renal failure exhibited decreased fraction of dose effectively absorbed and increased initial rate of absorption. The initial rate of absorption was inversely correlated with the creatinine clearance. The study disclosed evidence that absorption was modified in chronic renal failure.