Pharmacokinetics of Continuous Infusions of Althesin, Minaxolone and ICI 35 868 to Supplement Nitrous Oxide Anaesthesia in Man

Abstract

The steroid anaesthetics, Althesin or minaxolone (a new water soluble steroid), or ICI 35 868 (di-isopropylphenol) have been administered as continuous i.v. infusions to supplement nitrous oxide 67% in oxygen anaesthesia. We have defined the minimum infusion rate (MIR) for i.v. agents as that infusion rate which suppressed movement of the patient in response to the initial and to subsequent sustained surgical stimulation. Following premedication with morphine 0.15 mg kg⁻¹ and atropine 0.6 mg, MIR for 11 patients receiving Althesin was 18.0 ± 0.9 (SEM) μg min⁻¹ kg⁻¹ as total steroid, equivalent to 13.5 ± 0.7 μg min⁻¹ kg⁻¹ as alphaxalone. For nine patients receiving minaxolone MIR was 11.0 ± 0.5 μg min⁻¹ kg⁻¹, and for eight patients receiving ICI 35 868 51.3 ± 3.8 μg min⁻¹ kg⁻¹. There was no evidence of accumulation of any of the three drugs as the plasma concentrations remained steady between 30 min after starting the infusion, and the end of the infusion (range 55–245 min after the start). At the minimum infusion rates quoted above the plasma concentrations of the three i.v. agents were alphaxalone 1.9 ± 0.1 μg ml⁻¹; minaxolone 0.6 ± 0.05 μg ml⁻¹; ICI 35 868 1.54 ± 0.22 μg ml⁻¹.