RT Journal Article SR Electronic T1 EFFECTS OF ACUTE RENAL FAILURE ON THE PHARMACOKINETICS OF CHLORZOXAZONE IN RATS JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 776 OP 784 DO 10.1124/dmd.31.6.776 VO 31 IS 6 A1 Young Jin Moon A1 Ae Kyung Lee A1 Hye Chin Chung A1 Eun Jung Kim A1 So Hee Kim A1 Duk Chul Lee A1 Inchul Lee A1 Sang Geon Kim A1 Myung Gull Lee YR 2003 UL http://dmd.aspetjournals.org/content/31/6/776.abstract AB The purpose of this study is to report the changes of CYP2E1, CYP1A2, CYP2B1/2, CYP2C11, CYP3A23, and CYP3A2 expression and pharmacokinetics and tissue distribution of chlorzoxazone (CZX) and 6-hydroxychlorzoxazone (OH-CZX) in rats with acute renal failure induced by uranyl nitrate (U-ARF), and the role of CYP3A23 and CYP3A2 in the formation of OH-CZX in rats with U-ARF. In rats with U-ARF, CYP2C11 decreased to 20% of control, whereas CYP2E1 and CYP3A23 increased 2.3 and 4 times, respectively, compared with control. But expression of CYP1A2 and CYP2B1/2 was not changed by U-ARF. After i.v. administration of CZX at a dose of 20 mg/kg to rats with U-ARF, the areas under the plasma concentration-time curve from time 0 to time infinity (AUCs) of CZX and OH-CZX were significantly smaller and greater, respectively, than those in control rats. In rats with U-ARF, CZX was below the detection limit at 120 min in all rat tissues studied, whereas it was detected in all tissues of control rats at both 30 and 120 min. However, in control rats, OH-CZX was below the detection limit at both 30 and 120 min in all rat tissues except kidney, whereas it was detected in all tissues of rats with U-ARF at both 30 and 120 min. Based on results from supporting experiments with DDT and 2,2-bis(4-chlorophenyl)1,1-dichloroethylene treatment of rats, the contribution of CYP3A23 and CYP3A2 to the enhanced formation of OH-CZX in rats with U-ARF is likely to be negligible. The American Society for Pharmacology and Experimental Therapeutics