Relationship between plasma concentrations and pharmacological effects of labetalol

Abstract

In healthy normal subjects following the administration of labetalol the pharmacological effects were measured and compared with the plasma concentrations achieved. The inhibition of exercise induced tachycardia and inhibition of exercise induced increases in systolic pressure were significantly related to the administered dose of labetalol. Labetalol was rapidly absorbed from the gastrointestinal tract and peak plasma concentrations occurred two hours after oral administration. There was a linear correlation (r = 0.84) between the logarithm of the plasma concentration and the maximum inhibition of exercise tachycardia at two hours. After intravenous administration there was an immediate reduction in systolic and diastolic blood pressure with a concomitant small increase in heart rate. There was a rapid decline in the associated plasma concentration but the pharmacological effects were maintained in excess of two hours. Our findings are consistent with those of others who have studied the relationship between pharmacological events and plasma concentrations after single doses of other adrenoceptor blocking drugs.

Rate of onset of hypotensive effect of oral labetalol.

“…It has been previously shown, (Richards, Maconochie, Bland, Hopkins, Woodings & Martin, 1977) that labetalol is rapidly absorbed after oral administration, peak plasma concentrations occurring within 2 h. In addition, the same workers showed that there was a rapid decline in plasma concentrations although inhibition of exercise-induced tachycardia persisted longer than 4 h. Our observations would suggest that by 6 h after a single oral dose of 100 mg, blood pressure is returning towards pre-treatnent levels. After single doses of 400 mg, the duration of the hypotensive response was greater than after 100 mg.…”

Pharmacokinetics and pharmacodynamic studies of labetalol in hypertensive subjects.

“…There are no published data on the relative antihypertensive effects of the various isomers. Limited acute pharmacokinetic studies have been reported (Martin et al, 1976;Richards et al, 1977;Louis et al, 1978), suggesting variable bioavailability. The present report is a detailed study of the pharmacokinetics of labetalol following acute single dose administration of 100 and 200 mg.…”

Pharmacokinetics, beta‐adrenoceptor blockade and anti‐hypertensive action of labetalol during chronic oral treatment

“…Since the calculated plasma labetalol concentration midway between trough and peak levels (midpoint concentration) correlated significantly with plasma labetalol Css (Figure 5) this may provide a reliable estimate of the latter. Plasma labetalol Css correlated with the daily dose despite the extensive first-pass elimination which has been described following oral administration (Richards et al, 1977).…”

“…Considerable variation in plasma labetalol concentrations is likely to occur between individuals after oral administration because of extensive firstpass metabolism of the drug (Richards, Maconochie, Bland, Hopkins, Woodings & Martin, 1977) and to investigate this further, the pharmacokinetics and effects of labetolol were studied both between and within individual hypertensive patients.…”