PT - JOURNAL ARTICLE AU - Andrew A. Shaw AU - Stephen D. Hall AU - Michael R. Franklin AU - Raymond E. Galinsky TI - The Influence of <span class="sc">l</span>-Glutamine on the Depression of Hepatic Cytochrome P450 Activity in Male Rats Caused by Total Parenteral Nutrition AID - 10.1124/dmd.30.2.177 DP - 2002 Feb 01 TA - Drug Metabolism and Disposition PG - 177--182 VI - 30 IP - 2 4099 - http://dmd.aspetjournals.org/content/30/2/177.short 4100 - http://dmd.aspetjournals.org/content/30/2/177.full SO - Drug Metab Dispos2002 Feb 01; 30 AB - Total parenteral nutrition (TPN) bypasses the gut leading to intestinal and hepatic dysfunction, including decreased hepatic cytochrome P450 (P450) activity. Glutamine prevents the TPN-associated changes in gut function and morphology. This study examined the effect of glutamine supplementation on hepatic P450 activities in male Sprague-Dawley rats receiving continuous TPN. Animals received continuous lipid-free TPN for 7 days with 0, 0.1, or 4.5% glutamine. Surgical controls were allowed free access to rat chow. The Vmax/Kmratios (intrinsic clearance) for the formation of 4-hydroxymidazolam (CYP3A) were 12.8, 14.6, and 27.7 μl/min/mg for TPN treatment with 0, 0.1%, or 4.5% glutamine, respectively, compared with a chow-fed control (37.1 μl/min/mg). The corresponding values for 1′-hydroxymidazolam formation (CYP3A) were 3.7, 6.1, 11.7, and 15.2 μl/min/mg, respectively. The addition of glutamine to TPN similarly affected the formation rates for 2β- and 6β-hydroxytestosterone (CYP3A), and these metabolite formation rates were highly correlated (r = 0.865; p &lt; 0.001). The formation rates for 2α- and 16α-hydroxytestosterone (CYP2C) were also highly correlated (r = 0.892;p &lt; 0.001). Parenteral glutamine modified the TPN-associated suppression of CYP3A and CYP2C activities in adult male rats receiving TPN. The American Society for Pharmacology and Experimental Therapeutics