title: Lack of whole-body pharmacokinetic differences of halothane enantiomers in the rat.
abstract: BACKGROUND
  Halothane is made and used as a racemate (an equimolar mixture of R- and S- enantiomers). This study was initiated to determine whether there were demonstrable enantiomeric differences in the whole-body pharmacokinetics of halothane that might have significance for studies in which racemate is used.
  
  
  METHODS
  Adult male Wistar rats were exposed to halothane vaporized in the atmosphere of a closed constant volume chamber supplied with O2 commensurate with CO2 production. Concentrations of halothane enantiomers were measured by a specific gas chromatography-mass spectrometry method. Experiments were performed at four initial concentrations of halothane (0.1%, 0.5%, 1.0%, and 1.5% vol/vol). Enantiomeric differences in whole-body pharmacokinetics were assessed indirectly from the relative chamber atmosphere concentrations of halothane enantiomers.
  
  
  RESULTS
  Concentrations of halothane decreased biphasically. The initial more rapid decrease was interpreted as incorporating absorption, distribution, and clearance; the slower decrease was interpreted as principally incorporating metabolic clearance. The ratio of concentrations of the two halothane enantiomers and of the ratios of the respective areas under the concentration-time curves remained constant without differing from unity at any time at any concentration of halothane. The dose-normalized areas under the concentration-time curves for the concentrations 0.1%, 0.5%, and 1.0% did not differ; that for 1.5% was significantly greater, suggesting nonlinear clearance, but the values did not differ significantly between enantiomers at any concentration.
  
  
  CONCLUSIONS
  As there were no significant differences in concentrations of the two enantiomers in the chamber atmosphere, enantioselectivity was not demonstrated in the whole-body pharmacokinetics of halothane.
authors.affiliation: Department of Anaesthesia and Pain Management, The University of Sydney at Royal North Shore Hospital, St. Leonards, NSW, Australia. lmather@med.usyd.edu.au
authors.forename: L E
authors.initials: LE
authors.lastname: Mather
authors.forename: B L
authors.initials: BL
authors.lastname: Fryirs
authors.forename: C C
authors.initials: CC
authors.lastname: Duke
authors.forename: M J
authors.initials: MJ
authors.lastname: Cousins
mesh_terms: D018685:Anesthetics, Inhalation / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D019540:Area Under Curve; D001273:Atmosphere Exposure Chambers; D008401:Gas Chromatography-Mass Spectrometry; D006221:Halothane / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism
chemical_list: D018685:Anesthetics, Inhalation; D006221:Halothane