title: Kinetics of methoxyflurane biotransformation with reference to substrate inhibition.
abstract: The kinetics of biotransformation of methoxyflurane by rat hepatic microsomes in vitro was studied. The rate of 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 + 1) or an asymptotic curve with formula (see article) No substrate inhibition was observed. Total fluoride Vmax of 135.1 mmumol 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-containing metabolites. Phenobarbital induction caused qualitative as well as quantitative alteration in the biotransformation of methoxyflurane.
mesh_terms: D000769:Anesthesia, Inhalation; D000818:Animals; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004790:Enzyme Induction; D005459:Fluorides / Q000096:biosynthesis; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008733:Methoxyflurane / Q000008:administration & dosage / Q000378:metabolism*; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D008733:Methoxyflurane; D003577:Cytochrome P-450 Enzyme System; D005459:Fluorides; D010634:Phenobarbital