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 alpha-hydroxy-5 alpha-pregnane-11,20-dione) through the lung. Using the isolated rat lung perfused with a plasma substitute containing 14C-alphaxalone and 3H-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.
D000777:Anesthetics / Q000378:metabolism*; D000818:Animals; D007700:Kinetics; D008168:Lung / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D010477:Perfusion; D011277:Pregnanediones / Q000378:metabolism*; D011652:Pulmonary Circulation; D051381:Rats; D011955:Receptors, Drug / Q000378:metabolism
D000777:Anesthetics; D011277:Pregnanediones; D011955:Receptors, Drug; C006477:alphaxalone