Metabolism of the steroid anaesthetic alphaxalone by the isolated perfused rat lung.

Abstract

Abstract We have investigated the metabolism of the steroid anaesthetic, alphaxalone (3α-hydroxy-5α-pregnane-11, 20-dione), in the isolated rat lung perfused at 10ml min−1 with the plasma substitute, Haemaccel. When [14C]-alphaxalone was introduced into the perfusate during a 90 min recirculating perfusion, four metabolites appeared in the reservoir. We have identified two of these by gas chromatographic-mass spectrometric (GC-MS) methods as 3α,11-dihydroxy-5α-pregnane-20-one (metabolite 2), the major metabolite and 5α-pregnane-3α, 11,20-triol (metabolite 3); precise assignment of the stereochemistry at C11 and C20 was not possible. Following perfusion of up to 30 min with concentrations of alphaxalone ranging from 0.08 to 8.9 μM, we have measured metabolite 2 in both the lung tissue and in the reservoir. From this data we have obtained a Km of 0.25 μ and a Vmax of 7.8 nmol min−1 g dry lung−1. Extrapolating from reported plasma concentrations in humans, it would seem that this ability of the lung to metabolize alphaxalone would have tittle influence during induction of anaesthesia. However, it could significantly influence the concentration of alphaxalone in the cerebral circulation during administration of the considerably lower doses of alphaxalone used for sedation during regional anaesthesia.