Editorial Views  |   December 2016
CYP2B6*6 or Not CYP2B6*6—That Remains a Question for Precision Medicine and Ketamine!
Author Notes
  • From the Department of Anesthesiology and Critical Care Medicine (S.D.C.-S.), Department of Pediatrics (P.C.A.), and Department of Pediatrics and the Center for Applied Genomics (J.L., H.H.), The Children’s Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
  • Accepted for publication August 31, 2016.
    Accepted for publication August 31, 2016.×
  • Corresponding article on page 1103.
    Corresponding article on page 1103.×
  • Timothy J. Brennan, Ph.D., M.D., served as Handling Editor for this article.
    Timothy J. Brennan, Ph.D., M.D., served as Handling Editor for this article.×
  • Address correspondence to Dr. Cook-Sather: sather@email.chop.edu
Article Information
Editorial Views / Pharmacology
Editorial Views   |   December 2016
CYP2B6*6 or Not CYP2B6*6—That Remains a Question for Precision Medicine and Ketamine!
Anesthesiology 12 2016, Vol.125, 1085-1087. doi:10.1097/ALN.0000000000001399
Anesthesiology 12 2016, Vol.125, 1085-1087. doi:10.1097/ALN.0000000000001399
WHILE certainly not the dire existential question posed by Hamlet, could detailed knowledge of variants at CYP2B6 and other genetic loci bring precision medicine to the clinical dosing of ketamine? We believe that it will, but one nuanced by indication, route of administration, and other factors.
In this issue of Anesthesiology, Rao et al.1  present their work on the pharmacogenetics of ketamine in an attempt to better understand the etiologies of drug response variability, beginning with metabolism and pharmacokinetic differences.1  Cytochrome P450, family 2, subfamily B, member 6 (CYP2B6) is a high-affinity protein thought to predominate ketamine catabolism. The gene coding for CYP2B6 (CYP2B6) is highly polymorphic, with the common CYP2B6*6 (516G>T and 785A>G) variant, found largely in those of African descent, correlating with diminished hepatic CYP2B6 expression. Functionally, the associated gene product CYP2B6.6 and liver microsomes from CYP2B6*6 carriers both show reduced ketamine metabolism in vitro.2  Moreover, in chronic pain patients treated with 100 to 500 mg/24-h subcutaneous ketamine infusions, the CYP2B6*6 allele confers reduced steady-state ketamine clearance with gene dose effect.3 
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