Intra-patient comparison of the kinetics of alphaxalone and alphadolone in man

The disposition kinetics of the two steroid components of the anaesthetic agent Althesin have been determined in seven male patients undergoing peripheral vascular reconstructive surgery. The blood decay profiles for both alphaxalone and alphadolone can be described by an open two-compartment model, with a mean alpha phase half life of 1.9 min, and a mean beta phase half life of 34 min. The systemic clearances of alphaxalone and alphadolone were 1.52 l min-1 and 1.09 l min-1 respectively (p less than 0.01). The remaining derived kinetic parameters showed no difference for the two steroids except for a greater fraction of the alphadolone administered being present in the peripheral compartment at steady-state conditions (p less than 0.05). The relative contributions of metabolic loss to total loss of drug from the body were 0.56 and 0.85 at 10 min and 60 min respectively for alphaxalone, and 0.42 and 0.80 respectively for alphadolone (p less than 0.01 and p less than 0.05). Although alphadolone exists as the acetate in the proprietary formulation, rapid hydrolysis to the native steroid seems to occur in man. The exact site of this hydrolysis remains uncertain at present.