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Effects of intravenous lipid as a source of energy in parenteral nutrition associated hepatic dysfunction and lidocaine elimination: a study using isolated rat liver perfusion
Author(s) -
Zaman Nuzhat,
Tam Yun K.,
Jewell Lawrence D.,
Coutts Ronald T.
Publication year - 1997
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/(sici)1099-081x(199712)18:9<803::aid-bdd65>3.0.co;2-s
Subject(s) - lidocaine , steatosis , perfusion , metabolite , metabolism , parenteral nutrition , hydroxylation , drug metabolism , medicine , liver function , amino acid , chemistry , endocrinology , pharmacology , anesthesia , biochemistry , enzyme
The effects on liver function and hepatic lidocaine elimination using 20% Intralipid® as a source of non‐protein calories (30%) in parenteral nutrition were studied using an isolated rat liver perfusion procedure. Rats were randomly assigned to one of the three treatment groups: PNL group ( n =6), consisting of 16·94% dextrose, 2·46% Intralipid®, and 5·2% amino acids; PN group ( n =5), consisting of 24·2% dextrose and 5·2% amino acids; and CF group ( n =6), chow fed (rat chow and water). The rate of lidocaine metabolism was significantly reduced after 7 d in the two PN treated groups when compared to CF. Steatosis was observed in five out of six PNL treated animals and two out of five PN treated animals. Intrinsic clearance was reduced by 80% in the PNL group and by 60% in the PN animals ( p <0·05). Molar metabolite to drug ratios revealed significant reductions in N‐dealkylation, m ‐hydroxylation, and aryl methyl hydroxylation in groups PNL and PN; these values amounted to 67–92% ( p <0·05). These findings suggest that a dextrose–amino acid solution induced steatosis and reduced the rate of lidocaine metabolism. The incorporation of Intralipid® caused further deterioration. © 1997 John Wiley & Sons, Ltd.