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

Michael E. Jones; Terence E. Nicholas

doi:10.1007/BF01059270

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

Michael E. Jones, Terence E. Nicholas

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

Abstract

We have examined four mathematical systems modeling the transit of the steroid anesthetic alphaxalone (3α-hydroxy-5α-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.

Original language	English
Pages (from-to)	343-355
Number of pages	13
Journal	Journal of Pharmacokinetics and Biopharmaceutics
Volume	9
Issue number	3
DOIs	https://doi.org/10.1007/BF01059270
Publication status	Published - 1 Jun 1981

Keywords

alphaxalone
anesthetic
lung
steroid kinetics

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abstract = "We have examined four mathematical systems modeling the transit of the steroid anesthetic alphaxalone (3α-hydroxy-5α-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.",

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AU - Nicholas, Terence E.

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AB - We have examined four mathematical systems modeling the transit of the steroid anesthetic alphaxalone (3α-hydroxy-5α-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.

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

Abstract

Keywords

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