THE USE OF 2-HYDROXYPROPYL-BETA-CYCLODEXTRIN AS A VEHICLE FOR INTRAVENOUS ADMINISTRATION OF DEXAMETHASONE IN DOGS

Dexamethasone (Dex) was administered to 6 mongrel dogs in a dose of 5 mg/kg as the sodium salt of its phosphate ester or as an inclusion complex in 2-hydroxypropyl-β-cyclodextrin (HPCD). Blood and urine were collected and analyzed for dexamethasone by HPLC. The area under the plasma concentration time curve (AUC) of dexamethasone during the first hour was significantly greater after the administration of the Dex-HPCD complex compared to the phosphate ester prodrug (1.63 ± 0.13 vs 1.04 ± 0.10 μg h ml-1). In addition, the renal clearance (CLren) was significantly higher after administration of the HPCD form (0.91 ± 0.20 vs 0.52 ± 0.20 ml min-1 kg-1). There was no difference between treatments for other pharmacokinetic parameters of dexamethasone. Hence, intravenous injection of dexamethasone in HPCD allows direct administration of this poorly soluble steroid without any prodrug conversion. The higher plasma levels during the first hour after administration may be advantageous for the treament of emergency situations. © 1990.