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COMPARATIVE PHARMACOKINETICS OF d‐ AND l‐ALPHAMETHYLDOPA IN PLASMA, AQUEOUS HUMOR, AND CEREBROSPINAL FLUID IN RABBITS
Author(s) -
AUCLAIR E.,
LAUDE D.,
WAINER I. W.,
CHAOULOFF F.,
ELGHOZI J.L.
Publication year - 1988
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.1988.tb00640.x
Subject(s) - cerebrospinal fluid , pharmacokinetics , chemistry , kinetics , chromatography , aqueous humor , pharmacology , medicine , physics , quantum mechanics , ophthalmology
Summary— The 2 stereoisomers of alphamethyldopa (αMD) 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 αMD was observed in AH. A stereospecific active transport of αMD 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 αMD kinetic analyses illustrate the adaptation of AH and CSF removal procedures to the pharmacokinetic studies of the brain and ocular entry of AA isomers.