NCT00702715.

No abstract

No abstract

A lphaxalone is a neuroactive steroid anesthetic, formulated as the intravenous (IV) anesthetic Althesin (ALTH) and was used in that form from 1972 to 1984, when it was taken off the market owing to hypersensitivity reactions from the Cremophor El excipient. Alfaxan (ALF), a formulation of alphaxalone with hydoxypropyl-β-cyclodextrin, has been used in veterinary work. This study compares 2 preparations of alphaxalone, 1 using Cremophor EL (ALTH) and 1 using 7-sulfobutyl-ether-β-cyclodextrin (SBECD) in 0.9% saline (PHAX), as well as a preparation of propofol in the form of an injectable soya bean oil emulsion (PROP), in terms of anesthetic properties and therapeutic index (TI).Several experiments, approved by Monash Medical Centre Animal Ethics Committee B, were performed on a number of rats. After given doses of PROP, PHAX, or ALTH via internal jugular IV catheters, the rats were evaluated for normal righting reflex, response to a tail pinch, and time needed to recover from sedation, measured by the time the rat was able to walk on a rotating cylinder. Cardiovascular effects, including systolic and diastolic blood pressure, were measured using a noninvasive tail cuff blood pressure recorder on 3 groups of 5 rats, each receiving doses of the 3 drug preparations. Rats were also tested for lethal doses of the 3 agents, and the effect of SBECD on lethality was tested by giving 2 groups of 10 rats a lethal dose of ALTH 60 seconds after giving them a premedication of either 5.3 mL/kg 0.9% sodium chloride or 5.3 mL/kg 13% solution of SBECD in 0.9% sodium chloride solution.In terms of loss of righting reflex, the 50% effective dose (ED 50 ) (mean [95% confidence interval]) for PHAX and ALTH was 2.8 (2.2-4.3 mg/kg) and 3 (2.4-4.5 mg/kg), respectively. Both were found to be more potent than PROP (ED 50 = 4.6 [3.8-5.0 mg/kg]). Although the 2 formulations of alphaxalone had the same effect on systolic and diastolic blood pressures, the depression in blood pressure was substantially more with PROP than with PHAX. Dose escalation to more than 30 mg/kg of PROP caused death in the entire group of 10 rats, and a dose of 52 mg/kg of ALTH caused death of the 10 rats in the ALTH group. A PHAX dose of 52 mg/kg did not cause any rats to die and the 50% lethal dose for PHAX was found to be more than 84 mg/kg.