TY - JOUR T1 - METABOLISM OF R-(+)- AND S-(-)-PENTOBARBITAL BY HEPATIC MICROSOMES FROM MALE RATS JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 113 LP - 117 VL - 3 IS - 2 AU - JORDAN L. HOLTZMAN AU - JOHN A. THOMPSON Y1 - 1975/03/01 UR - http://dmd.aspetjournals.org/content/3/2/113.abstract N2 - Hepatic microsomes from male rats hydroxylate R-(+)- and S-(-)-[2-14C]pentobarbital to the diastereoisomeric 3'-alcohols: metabolite I (1'RS, 3'SR)- and metabolite II (1'RS, 3'RS)-5-ethyl-5-(3'-hydroxy-1'methylbutyl) barbituric acids. The rate is linear up to 1.5 mg of microsomal protein per ml of incubation mixture and for up to 16 min. The metabolism of R-(+)-pentobarbital led to production of nearly equal quantities of metabolites I and II with a total hydroxylation of 1.08 nmol/min/mg of protein. On the other hand, the S-(-)-pentobarbital gave 3- to 5-fold less of metabolite I than II and a total hydroxylation of 1.42 nmol/min/mg of protein. The KM values for formation of metabolite I were 381 µM from R-(+)- and 241µ M from the S-(-)-pentobarbital, while for metabolite II they were 115 µM from R-(+)and 68 µM from S-(-)-pentobarbital. These data suggest that there are at least two enzymes catalyzing the hydroxylation of pentobarbital, one to give metabolite II and another or others to give metabolite I. Copyright © 1975 by The American Society for Pharmacology and Experimental Therapeutics ER -