COMPARATIVE PHARMACOKINETICS OF 2 DIASTEREOISOMERS DEXAMETHASONE AND BETAMETHASONE IN PLASMA AND CEREBROSPINAL-FLUID IN RABBITS

The two diastereoisomers dexamethasone (DXM) and betamethasone (BTM) w ere infused at two different doses (2, 10 mg.kg(-1)) in anesthetized r abbits. Samples of plasma and cerebrospinal fluid were collected over a 180-min period. Steroid concentrations were measured by high perform ance liquid chromatography. The terminal half life (85.7 +/- 20.8 min and 102.2 +/- 29.6 min for DXM; 117.6 +/- 19.8 min and 118.5 +/- 15.8 min for BTM) and the mean residence time (121.4 +/- 27.7 min and 146.1 +/- 41.3 min for DXM; 168.6 +/- 28.1 min and 172.2 +/- 20.6 min for B TM) were unchanged between the doses. Dose-dependent changes in the ar ea under the curve normalized by the dose, then volume distribution an d clearance were observed. The average percentage of DXM and BTM bound to plasma proteins were 78.1 +/- 11.5% and 88.3 +/- 5.1% respectively at the lower dose, and decreased significantly with 10 mg.kg(-1). DXM appeared more rapidly in the CSF, the highest concentrations of DXM w ere obtained within 15 min after the end of the injection. The CSF lev els were lower than that of plasma unbound and the passage through the blood-brain barrier was saturable. These results will complicate phar macokinetic and pharmacodynamic analysis.