Biotransformation of ketamine, (Z)-6-hydroxyketamine, and (E)-6-hydroxyketamine by rat, rabbit, and human liver microsomal preparations.
1. (Z)- and (E)-6-Hydroxyketamine have been synthesized and their metabolism by hepatic microsomal preparations studied to elucidate the metabolism of ketamine. 2. Both 6-hydroxyketamines are exclusively converted to 6-hydroxy-norketamines by N-demethylation. The g.l.c. retention properties and mass spectral characteristics of these 6-hydroxy-norketamines were used to confirm the structures of ketamine metabolites. 3. Ketamine is converted to norketamine, 4-, 5- and 6-hydroxynorketamines and possibly 4- and 6-hydroxyketamines in hepatic microsomal preparations from rats, rabbits and man. Norketamine is the major metabolite in all species tested. 4. 6-Hydroxynorketamine is the major hydroxylated metabolite and is found only in the (Z)-form in the species examined. 5. The metabolism of ketamine and the 6-hydroxy-ketamines is greatly increased after phenobarbital pretreatment of rats and rabbits.
Woolf
T F
TF
Department of Pharmacology, University of California, San Francisco 94143.
Adams
J D
JD
D000818:Animals; D001711:Biotransformation; D002849:Chromatography, Gas; D006801:Humans; D066298:In Vitro Techniques; D007649:Ketamine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013057:Spectrum Analysis; D013237:Stereoisomerism
D007649:Ketamine; C053741:6-hydroxyketamine; C033419:norketamine