PT - JOURNAL ARTICLE AU - Gregory S. Gorman AU - Lori Coward AU - Corenna Kerstner-Wood AU - Lea Cork AU - Izet M. Kapetanovic AU - Wayne J. Brouillette AU - Donald D. Muccio TI - In Vitro Metabolic Characterization, Phenotyping, and Kinetic Studies of 9cUAB30, a Retinoid X Receptor-Specific Retinoid AID - 10.1124/dmd.106.013938 DP - 2007 Jul 01 TA - Drug Metabolism and Disposition PG - 1157--1164 VI - 35 IP - 7 4099 - http://dmd.aspetjournals.org/content/35/7/1157.short 4100 - http://dmd.aspetjournals.org/content/35/7/1157.full SO - Drug Metab Dispos2007 Jul 01; 35 AB - The present study was conducted to compare the in vitro phase I and phase II metabolic profiles of (2E,4E,6Z,8E)-8-(3′,4′-dihydro-1′(2′H)-naphthalen-1′-ylidene)-3,7-dimethyl-2,4,6-octatrienoic acid (9cUAB30) in human, rat, and dog microsomes and to characterize and identify the associated metabolic kinetics and specific isozymes from human liver microsomes (HLM) responsible for metabolism, respectively. Data from these experiments revealed that nine (M1–M9) phase I metabolites along with a single glucuronide conjugate were observed across the species investigated. With the exception of glucuronidation, no evidence of metabolism was detected for phase II enzymes (data not shown). Significant differences between species with regard to metabolic profile, stability, and gender were noted. For the eight phase I metabolites detected in HLM, the specific isozymes responsible for the biotransformations were CYP2C8, CYP2C9, and CYP2C19, with minor contributions from CYP1A2 and CYP2B6. For the glucuronide conjugate, UGT1A9 was the major catalyzing enzyme, with a minor contribution from UGT1A3. Kinetic analysis of eight of the detected metabolites indicated that four seemed to follow classical hyperbolic kinetics, whereas the remaining four showed evidence of either autoactivation or substrate inhibition. The American Society for Pharmacology and Experimental Therapeutics