Influence of Maternal Plasma Protein Binding on Fetal Unbound Plasma Concentration of Propranolol in the Pregnant Ewe

Pharmacokinetics/pharmacodynamics of labetalol in three pregnant ewes using high‐performance liquid chromatography

“…8 We describe here the main results of a study using a similar preparation, which had three major objectives: firstly, to determine the pharmacokinetics of labetalol in the pregnant ewe; secondly, to determine the pharmacological action of labetalol in the pregnant ewe and the fetus on their blood pressure and heart rate; and, lastly, to assess the applicability of pharmacodynamic/ pharmacokinetic modelling techniques to the profile of labetalol during pregnancy. In order to analyse the plasma concentrations of labetalol adequately, a high-performance liquid chromatographic analysis method has been developed, based upon a liquid-liquid extraction of the analyte from plasma and subsequent chromatographic separation using a cyano-bonded stationary phase.…”

“…Labetalol (2-hydroxy-5-[ 1 -hydroxy-2-( 1 -methyl-3-phenylpropyl-amino)ethyl]benzamide) is a specific and competitive antagonist at both a-and 8adrenoceptors, which has been shown to be effective in the treatment of hypertension and angina pectoris as well as the management of hypertension occurring during Unfortunately, only little information is available on both the pharmacodynamic action and pharmacokinetics of labetalol in f e t u~e s .~ Nowadays, the concept of pharmacodynamic/pharmacokinetic modelling for antihypertensive drugs is receiving much a t t e n t i~n .~~' The chronically cannulated pregnant sheep preparation has been used for the evaluation of pharmacokinetic parameters of propranolol in both mother and fetus. 8 We describe here the main results of a study using a similar preparation, which had three major objectives: firstly, to determine the pharmacokinetics of labetalol in the pregnant ewe; secondly, to determine the pharmacological action of labetalol in the pregnant ewe and the fetus on their blood pressure and heart rate; and, lastly, to assess the applicability of pharmacodynamic/ pharmacokinetic modelling techniques to the profile of labetalol during pregnancy. In order to analyse the plasma concentrations of labetalol adequately, a high-performance liquid chromatographic analysis method has been developed, based upon a liquid-liquid extraction of the analyte from plasma and subsequent chromatographic separation using a cyano-bonded stationary phase.…”