Kinetics of Methoxyflurane Biotransformation with Reference to Substrate Inhibition

The kinetics of biotransformation of methoxyflurane by rat hepatic microsomes in vitro was studied. The rate or biotransformation as measured by analysis of metabolites continued to increase even at near-saturation concentrations of the anesthetic. Methoxyflurane biotransformation followed either an unbounded curve with empirical formula y = a ln(bx + I) or an asymptotic curve with formula y = x/ax+b No substrate inhibition was observed, Total fluoride Vmax of 135.1 mμmol F-/mg protein/30‘ was increased to 931.9 by phenobarbital induction: free fluoride Vmax from 39.2 to 403.2. Thus, enzyme induction shifted biotransformation to the production of greater amounts of inorganic free fluoride metabolites than organic fluoride-contaning metabolites, Phenobarbital induction caused qualitative as well as quantitative alteration in the biotransformation of methoxyflurane.