COMPARATIVE PHARMACOKINETICS OF d‐ AND l‐ALPHAMETHYLDOPA IN PLASMA, AQUEOUS HUMOR, AND CEREBROSPINAL FLUID IN RABBITS

Abstract

The 2 stereoisomers of alphamethyldopa (alpha MD) were separately injected IV at 3 different doses (3, 10, 30 mg/kg) in anesthetized rabbits. Samples of plasma, aqueous humor (AH), and cerebrospinal fluid (CSF) were collected over a 300-min period. The concentration of the aminoacid (AA) was determined by liquid chromatography and electrochemical detection. Parameters obtained from kinetic analyses of the plasma concentrations were close to the values reported in other species. Linear elimination kinetics were observed in the dose range studied. A marked dose-dependent entry of alpha MD was observed in AH. A stereospecific active transport of alpha MD was evidenced in the AH since the concentration of the L-isomer reached values above the plasma levels. CSF entry of the AA was small when compared to AH kinetics. A limited passive diffusion of the AA in the brain could account for this phenomenon. However, greater availability of the L-stereoisomer was still observed in CSF. These alpha MD kinetic analyses illustrate the adaptation of AH and CSF removal procedures to the pharmacokinetic studies of the brain and ocular entry of AA isomers.

REM sleep and catecholamine excretion: a study in elite athletes

“…However, there are studies that report strong correlations between peripheral and central levels of catecholamines and additional experimental evidence of similar monoamine levels in both the cerebrospinal¯uid and plasma (Auclair et al 1988;Chaoulo 1993;Grace et al 1998;Sarmento 1991). This literature indicates a positive correlation between central and peripheral sympathetic activity.…”

The therapeutic promise of single enantiomers: introduction

“…The l-enantiomer of -methyldopa undergoes active and selective transport in the rabbit eye. As shown in Table 1 (Auclair et al, 1988), the maximum concentration (C max ) attained with l--methyldopa is more than double that attained with the d-enantiomer, while the initial entry rate is some 4.5 times more rapid with the l-enantiomer. The area under the curve (AUC; a measure of drug exposure) also showed a statistically signi®cant increase with the administration of the l-enantiomer, compared with d--methyldopa.…”