Mean steady‐state plasma concentrations of labetalol in patients undergoing antihypertensive therapy.

Sanders, GL; Routledge, PA; Ward, Amie S.; Davies, D.M.; Rawlins,

doi:10.1111/j.1365-2125.1979.tb04772.x

Cited by 7 publications

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References 5 publications

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“…There is some evidence of a relationship between steady-state plasma labetalol levels and blood pressure control in that most, but not all, patients with lower steady-state levels on a given dose required higher maintenance doses to achieve blood pressure However, in the study of Sanders and colleagues, no correlation was found between the steady-state concentration of labetalol and the antihypertensive response. 61 In this study the degree of beta-adrenoceptor blockade, measured as isoproterenol CD, , , paralleled the changes in plasma labetalol concentration.…”

Section: Pharmacodynamic Propertiessupporting

confidence: 53%

Labetalol: A Review of Its Pharmacology, Pharmacokinetics, Clinical Uses and Adverse Effects

1983

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Labetalol is a combined alpha- and beta-adrenoceptor blocking agent for oral and intravenous use in the treatment of hypertension. It is a nonselective antagonist at beta-adrenoceptors and a competitive antagonist of postsynaptic alpha 1-adrenoceptors. Labetalol is more potent at beta that at alpha 1 adrenoceptors in man; the ratio of beta-alpha antagonism is 3:1 after oral and 6.9:1 after intravenous administration. Labetalol is readily absorbed in man after oral administration, but the drug, which is lipid soluble, undergoes considerable hepatic first-pass metabolism and has an absolute bioavailability of approximately 25%. There are no active metabolites, and the elimination half-life of the drug is approximately 6 hours. Unlike conventional beta-adrenoceptor blocking drugs without intrinsic sympathomimetic activity, labetalol, when given acutely, produces a decrease in peripheral vascular resistance and blood pressure with little alteration in heart rate or cardiac output. However, like conventional beta-blockers, labetalol may influence the renin-angiotensin-aldosterone system and respiratory function. Clinical studies have shown that the antihypertensive efficacy of labetalol is superior to placebo and to diuretic therapy and is at least comparable to that of conventional beta-blockers, methyldopa, clonidine and various adrenergic neuronal blockers. Labetalol administered alone or with a diuretic is often effective when other antihypertensive regimens have failed. Studies have shown that labetalol is effective in the treatment of essential hypertension, renal hypertension, pheochromocytoma, pregnancy hypertension and hypertensive emergencies. In addition, preliminary studies indicate that labetalol may be of value in the management of ischemic heart disease. The most troublesome side effect of labetalol therapy is posture-related dizziness. Other reported side effects of the drug include gastrointestinal disturbances, tiredness, headache, scalp tingling, skin rashes, urinary retention and impotence. Side effects related to the beta-adrenoceptor blocking effect of labetalol, including asthma, heart failure and Raynaud's phenomenon, have been reported in rare instances.

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Section: Pharmacodynamic Propertiessupporting

confidence: 53%

Labetalol: A Review of Its Pharmacology, Pharmacokinetics, Clinical Uses and Adverse Effects

1983

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“…4) and this probably explains why some investigators have claimed that no such relationship exists (Lund-Johansen and Bakke, 1979;Sanders et al, 1979). However, McNeil (1981), examining the dose response-relationship in patients receiving twice daily doses ranging from 200 to 1200mg, found a clear relationship between the plasma drug concentration and the fall in blood pressure, especially in the upright position ( fig.…”

mentioning

confidence: 92%

Clinical Pharmacokinetics of Labetalol

McNeil

Louis

1984

Clinical Pharmacokinetics

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Labetalol was the first of a new class of antihypertensive drugs with both alpha- and beta-adrenoceptor blocking properties present in the same molecule. Its efficacy has been confirmed by double-blind studies in the treatment of all grades of hypertension and in angina pectoris. The drug's major dose-related side effect is postural hypotension. The clinical formulation of labetalol consists of equal proportions of 4 optical isomers. One of these (the RR isomer) is probably responsible for the drug's beta-adrenoceptor blockade and another (the SR isomer) produces most of the alpha-blockade. Most of the presently available pharmacokinetic information concerning labetalol is from studies utilising a fluorimetric assay but this has recently been superseded by more specific high-pressure liquid chromatographic (HPLC) procedures. Labetalol is absorbed rapidly after oral administration with peak plasma concentrations generally being achieved within 2 hours. The bioavailability varies from 10% to over 80% in different subjects. Average bioavailability has been reported to correlate with age, with values of approximately 30% in the 30- to 40-year age group and approximately 65% at 80 years. There is also evidence that the bioavailability increases moderately when the drug is taken with food. About 50% of the drug is bound in the plasma. The apparent volume of distribution at equilibrium varies from approximately 200 to over 800L, suggesting that concentration of labetalol occurs in extravascular sites. Radiochemical analysis in animals has shown high levels of accumulation in the lung, liver and kidney with little present in brain tissue. This is in keeping with the relatively low lipid solubility of labetalol. The half-life of labetalol in plasma is 3 to 3.5 hours. The drug is eliminated mainly by hepatic metabolism with the production of several biologically inactive glucuronides which in turn are excreted in the urine and bile. Approximately 85% of labetalol in the blood is removed during a single passage through the liver; thus, like propranolol, labetalol's clearance is probably flow dependent (i.e. it is sensitive to alterations in hepatic blood flow). Small doses of the drug (i.e. 300mg daily) have been shown to reduce antipyrine clearance by approximately 15%, and further studies are necessary to determine whether high doses produce a greater, possibly clinically significant, inhibition of mixed-function oxidase activity. After both single doses and during long term treatment the plasma concentration-time profile of labetalol shows marked variation between different individuals.(ABSTRACT TRUNCATED AT 400 WORDS)

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