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.
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.
Zaman
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Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
Tam
Y K
YK
Jewell
L D
LD
Coutts
R T
RT
D000596:Amino Acids / Q000008:administration & dosage; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D005217:Fat Emulsions, Intravenous / Q000008:administration & dosage* / Q000009:adverse effects; D005234:Fatty Liver / Q000139:chemically induced*; D005947:Glucose / Q000008:administration & dosage; D006900:Hydroxylation; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D008012:Lidocaine / Q000378:metabolism* / Q000493:pharmacokinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010288:Parenteral Nutrition / Q000009:adverse effects*; D010477:Perfusion; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D000596:Amino Acids; D015415:Biomarkers; D005217:Fat Emulsions, Intravenous; D008012:Lidocaine; D005947:Glucose