The pharmacokinetics of metabolism of inhalation anaesthetics. A simulation study

The non-steady state metabolism of inhalation anaesthetics during anaesthesia and recovery was simulated with a linear and non-linear whole body compartmental model. These two models were studied for nine anaesthetics during 1-MAC anaesthesias lasting 1, 4 and 8 h and recovery from 5 to 10 days. Both models demonstrated significant metabolism for several days following anaesthesia. For the linear model, both the percentage and the molar quantity of anaesthetic metabolized increased with increased duration of anaesthesia, increased anaesthetic fat solubility and increased assumed rate of hepatic metabolism. For the non-linear model, the duration of anaesthesia had little effect on the percentage metabolized but demonstrated increased molar quantities of anaesthetic metabolized with increased duration of anaesthesia and increased fat solubility. The agreement between the results obtained from the non-linear model and experimental data in the literature suggests that many inhalation anaesthetics belong to a class of xenobiotics whose biotransformation is limited by the same or similar non-linear rate-limiting step(s). A difference in the quantities of anaesthetic metabolized would be a direct consequence of the tissue solubilities of the anaesthetic.