Labetalol disposition and concentration‐effect relationships during pregnancy.

Pc, Rubin; Butters, L; Kelman, Andrew W.; Fitzsimons, C; Reid, JL

doi:10.1111/j.1365-2125.1983.tb01531.x

Cited by 48 publications

(14 citation statements)

References 16 publications

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“…The pharmacokinetic disposition of the drug in pregnant patients has been studied by Rubin et al (1983). In 7 women who were studied during the third trimester and again 3 to 4 months post partum there was no clinically significant difference in clearance or half-life, suggesting that the dosage regimens appropriate for pregnant patients are probably similar to those recommended for non-pregnant sUbjects.…”

Section: Pregnancy and The Puerperiummentioning

confidence: 98%

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information concerning labetalol is from studies utilising a fluorimetric assay but this has recently been superseded by more specific high-pressure liquid chromatographic (HPLC) procedures.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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Section: Pregnancy and The Puerperiummentioning

confidence: 98%

Clinical Pharmacokinetics of Labetalol

McNeil

Louis

1984

Clinical Pharmacokinetics

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“…The pharmacodynamics of labetalol have been fairly well investigated in nonpregnant and pregnant women [6][7][8]. After a single dose of labetalol, the plasma concentration versus time profile shows marked variation between individuals and there is no uniform relationship between the plasma concentra tion and the fall in BP; it has been concluded that individual sensitivity to the drug plays a major role in determining the BP response [81-In this study, the antihypertensive effect of labetalol in the normotensive subjects was clear-cut.…”

Section: Discussionmentioning

confidence: 99%

Single Dose of Labetalol in Normotensive Pregnancy: Effects on Maternal Hemodynamics and Uterine and Fetal Flow Velocity Waveforms

Pirhonen¹,

Erkkola²,

Mäkinen³

et al. 1991

Neonatology

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The short-term effect of 0.8 mg/kg of intravenous bolus of labetalol upon maternal and fetal hemodynamics was investigated in 10 healthy women at 38 weeks of gestation admitted to the hospital for elective cesarean section. The maximum effect occurred within 35 min after labetalol. At that point, the mean arterial pressure had decreased by 16%, and a slight decrease was observed in maternal heart rate. As to the flow velocity waveforms, no significant change was found in mean systolic/diastolic (S/D) ratio of uterine artery, umbilical artery or fetal middle cerebral artery. However, in 2 subjects with a large decrease in blood pressure also the uterine artery S/D ratio decreased.

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“…The elimination half-life after intravenous administration in pregnant hypertensive patients is similar to that seen with oral administration (62). The elimination half-life at steady state is significantly less than that seen in nonpregnant individuals (6-8 hours) (63), and for this reason, more frequent dosing is recommended in pregnancy (4-6 hours).…”

Section: Labetalolmentioning

confidence: 85%

Cerebral Hemodynamics in Preeclampsia: Cerebral Perfusion and the Rationale for an Alternative to Magnesium Sulfate

Belfort

Clark

Sibai

2006

Obstetrical & Gynecological Survey

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After completion of this article, the reader should be able to recall that hypertensive diseases of pregnancy contribute a significant portion of today's maternal mortality, explain that methods of preventing eclampsia are not applicable worldwide, and state that understanding of the pathophysiology of preeclampsia/eclampsia may assist in developing safe and effective medications that can be used universally.

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Labetalol disposition and concentration‐effect relationships during pregnancy.

Cited by 48 publications

References 16 publications

Clinical Pharmacokinetics of Labetalol

Clinical Pharmacokinetics of Labetalol

Single Dose of Labetalol in Normotensive Pregnancy: Effects on Maternal Hemodynamics and Uterine and Fetal Flow Velocity Waveforms

Cerebral Hemodynamics in Preeclampsia: Cerebral Perfusion and the Rationale for an Alternative to Magnesium Sulfate

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