Ketamine distribution described by a recirculatory pharmacokinetic model is not stereoselective

Background: Differences in the pharmacokinetics of the enantiomers df ketam ine have been reported. The authors sought to determine whether these diffe rences 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 (antipyr ine) were determined along with S-(+)- and R-(-)-ketamine in five mongrel d ogs. The dogs were studied while anesthetized with 2.0% halothane, Marker a nd drug dispositions were described by recirculatory pharmacokinetic models based on frequent early and less-frequent later arterial blood samples, Th ese models characterize pulmonary uptake and the distribution of cardiac ou tput into parallel peripheral circuits. Results: Plasma elimination clearance of the S-(+)-ketamine enantiomer, 29. 9 ml.min(-1).kg-1, was higher than that of the R-(-)-enantiomer, 22.2 ml.mi n(-1).kg(-1). The apparent pulmonary tissue volumes of the ketamine S-(+) a nd R-(-)-enantiomers (0.31 l) did not differ and was approximately twice th at of antipyrine (0.16 l), The peripheral tissue distribution volumes and c learances and the total volume of distribution (2.1 l/kg) were the same for both stereoisomers when elimination clearances were modeled from the rapid ly equilibrating peripheral compartment, Conclusions: Although the elimination clearance of S-(+)-ketamine is 35% gr eater than that of the R-(-)-enantiomer, there is no difference in the appa rent 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.