Phencyclidine Continuous Dosing Produces a Treatment Time- Dependent Regulation of Rat CYP2C11 Function, Protein Expression and mRNA Levels1

These studies determined the effects of continuous phen-cyclidine (PCP) administration on cytochrome P450 2C11 (CYP2C11) function, protein expression and mRNA levels. Male Sprague-Dawley rats received s.c. PCP infusions (18 mg/kg/ day) for 1, 3, 10 or 20 days (n 5 4 per group). Control animals received saline infusions for 3 or 20 days. Livers were collected 24 hr postinfusion, a time when PCP was completely cleared from the animals. In microsomes from the 1- and 3-day PCP infusions, there was a significant decrease (P,.05) in CYP2C11 protein expression (61 and 46 % of control values, respectively) and in CYP2C11-mediated metabolism of PCP to a reactive metabolite (36 and 41 % of control values). Both protein expression and PCP metabolite formation had returned to normal by 10 days of continuous PCP infusion. CYP2C1