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

E. AUCLAIR, D. LAUDE, I. W. WAINER, F. CHAOULOFF, J.L. ELGHOZI
Fundamental & Clinical Pharmacology. 1988-07-08; 2(4): 283-293
DOI: 10.1111/j.1472-8206.1988.tb00640.x

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Auclair E(1), Laude D, Wainer IW, Chaouloff F, Elghozi JL.

Author information:
(1)Centre de Recherches Merck, Sharp and Dohme-Chibret, Route de Marsat, Riom.

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.

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