title: Effects of parenteral nutrition on hepatic elimination of lidocaine: a study using the isolated perfused rat liver.
abstract: The effects of acute and a short-term (7 days) parenteral nutrition (PN, consisting of 24.2% dextrose and 5.2% amino acids) on hepatic lidocaine elimination were studied using an isolated perfused rat liver preparation. In the acute study, lidocaine was coinfused with PN solution or normal saline at 0.123 ml/min for 80 min. There was no significant difference in hepatic lidocaine elimination between control and PN-treated groups (six per group). In the post-PN study, only lidocaine was infused for 80 min. Lidocaine hepatic clearance and extraction ratio were reduced by 29.8 and 31.1% (P less than .05), respectively, compared to what occurred in livers isolated from control animals with free access to standard laboratory rat-chow and water (six per group). Mass balance at steady state showed that recovery was higher for lidocaine (46.58 +/- 7.28% vs. 25.56 +/- 5.59%) and lower for N-(N,N-diethylglycyl)-2-hydroxymethyl-6-methylaniline (0.21 +/- 0.01% vs. 2.75 +/- 0.58%) in the PN group compared to chow-fed controls. Recoveries of other lidocaine metabolites: N-(N-ethylglycy)-2,6-xylidine, 3-hydroxylidocaine, 3-hydroxy-N-(N-ethylyglycyl)-2,6-xylidine and N-(N-ethylglycyl)-2-hydroxymethyl-6-methylaniline were similar in the PN- and chow-fed group. These findings suggest that acute PN infusion has no effect on lidocaine metabolism, and that the impaired hepatic lidocaine elimination after 7-days of PN occurs as a result of selective inhibition of hepatic enzyme activities such as those involved in aryl methyl hydroxylation and in other unidentified metabolic pathway(s).
authors.affiliation: Faculty of Pharmacy & Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Ke
authors.forename: Y K
authors.initials: YK
authors.lastname: Tam
authors.forename: W W
authors.initials: WW
authors.lastname: Koo
authors.forename: M R
authors.initials: MR
authors.lastname: Gray
authors.forename: R T
authors.initials: RT
authors.lastname: Coutts
mesh_terms: D000596:Amino Acids / Q000097:blood; D000818:Animals; D006900:Hydroxylation; D008012:Lidocaine / Q000493:pharmacokinetics*; D008099:Liver / Q000378:metabolism*; D008297:Male; D010288:Parenteral Nutrition; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D000596:Amino Acids; D008012:Lidocaine