title: Ketamine distribution described by a recirculatory pharmacokinetic model is not stereoselective.
abstract: BACKGROUND
  Differences in the pharmacokinetics of the enantiomers of ketamine have been reported. The authors sought to determine whether these differences extend to pulmonary uptake and peripheral tissue distribution and to test the hypothesis that tissue distribution of the stereoisomers differs because of carrier-mediated drug transport.
  
  
  METHODS
  The dispositions of markers of intravascular space and blood flow (indocyanine green, ICG) and total body water and tissue perfusion (antipyrine) were determined along with S-(+)- and R-(-)-ketamine in five mongrel dogs. The dogs were studied while anesthetized with 2.0% halothane. Marker and drug dispositions were described by recirculatory pharmacokinetic models based on frequent early and less-frequent later arterial blood samples. These models characterize pulmonary uptake and the distribution of cardiac output into parallel peripheral circuits.
  
  
  RESULTS
  Plasma elimination clearance of the S-(+)-ketamine enantiomer, 29.9 ml x min(-1) x kg(-1), was higher than that of the R-(-)-enantiomer, 22.2 ml x min(-1) x kg(-1). The apparent pulmonary tissue volumes of the ketamine S-(+) and R-(-)-enantiomers (0.31 l) did not differ and was approximately twice that of antipyrine (0.16 l). The peripheral tissue distribution volumes and clearances and the total volume of distribution (2.1 l/kg) were the same for both stereoisomers when elimination clearances were modeled from the rapidly equilibrating peripheral compartment.
  
  
  CONCLUSIONS
  Although the elimination clearance of S-(+)-ketamine is 35% greater than that of the R-(-)-enantiomer, there is no difference in the apparent pulmonary tissue volume or peripheral tissue distribution between the stereoisomers, suggesting that physicochemical properties of ketamine other than stereoisomerism determine its perfusion-limited tissue distribution.
authors.affiliation: Department of Anesthesiology, Northwestern University Medical School, Chicago, Illinois, USA. tkhenthorn@ski.uhcolorado.edu
authors.forename: T K
authors.initials: TK
authors.lastname: Henthorn
authors.forename: T C
authors.initials: TC
authors.lastname: Krejcie
authors.forename: C U
authors.initials: CU
authors.lastname: Niemann
authors.forename: C
authors.initials: C
authors.lastname: Enders-Klein
authors.forename: C A
authors.initials: CA
authors.lastname: Shanks
authors.forename: M J
authors.initials: MJ
authors.lastname: Avram
mesh_terms: D000465:Algorithms; D000778:Anesthetics, Dissociative / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D000983:Antipyrine; D019540:Area Under Curve; D004396:Coloring Agents; D004285:Dogs; D007208:Indocyanine Green; D007649:Ketamine / Q000737:chemistry / Q000493:pharmacokinetics*; D008168:Lung / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D013237:Stereoisomerism; D014018:Tissue Distribution
chemical_list: D000778:Anesthetics, Dissociative; D004396:Coloring Agents; D007649:Ketamine; D007208:Indocyanine Green; D000983:Antipyrine