The pharmacokinetics of the intravenous steroid anesthetic alphaxalone in the isolated perfused rat lung

We have examined four mathematical systems modeling the transit of the steroid anesthetic alphaxalone (3-hydroxy-5-pregnane-11,20-dione) through the lung. Using the isolated rat lung perfused with a plasma substitute containing¹⁴C-alphaxalone and³H-dextran, we have obtained results that are incompatible with models involving (a) anatomical variations in the microcirculation, (b) high solubility, or (c) specific binding. We develop a stochastic model of a physical process analogous to the sequence of events that takes place in a chromatography column. This model closely fits the experimental data and predicts a peak effluent concentration of alphaxalone that may occur after washout with several exclusion volumes. It represents a delay with the pulmonary compartment that may explain a difference in induction times observed between various intravenous anesthetic agents.