Effects of light-exposed parenteral nutrition on hepatic function and lidocaine metabolism: a study using isolated rat liver perfusion.
Effects of light-exposed parenteral solutions on hepatic function and lidocaine metabolism were studied. Male rats (190-220 g) were randomly assigned to one of the three isocaloric treatment groups: parenteral nutrition (PN) (+L) group (n = 6), animals received a solution of 24.2% dextrose and 5.2% amino acids with light exposure; PN(-L) group (n = 5), animals received the same solution without light exposure; and CF group, chow-fed animals (n = 6) that received rat chow and water. Average energy intake in these animals was approximately 33 kcal/100 g/d. Lidocaine metabolism was studied in livers isolated from animals 7 d after treatment. Liver morphology indicated that five livers from PN(+L) animals developed steatosis. The lidocaine metabolism rate was the slowest in PN(+L) animals; this is marked by changes in the steady state levels (% dose) of lidocaine [PN(+L), 47.9 +/- 17.6; PN(-L), 25.9 +/- 2.1; versus CF, 11.3 +/- 5.3; p < 0.05]. The extraction ratio and intrinsic clearance values were reduced by 41 and 86% in PN(+L) group and 16 and 70% in PN(-L) group, respectively, when compared with CF (p < 0.05). Metabolite to drug ratios indicated that N-dealkylation, ring-hydroxylation, and aryl methyl hydroxylation of lidocaine were severely impaired, particularly in the PN(+L) animals. The extents of reduction in metabolic pathways were in the ranges 79-95% in the PN(+L) group and 44-90% in the PN(-L) (p < 0.05). These findings suggest that parenteral nutrition infusion induces steatosis and reduces the rate of lidocaine metabolism and exposure of parenteral nutrition solutions to light exacerbates this change.
Zaman
N
N
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 / Q000097:blood; D000818:Animals; D001835:Body Weight / Q000502:physiology; D066298:In Vitro Techniques; D008012:Lidocaine / Q000378:metabolism* / Q000493:pharmacokinetics / Q000652:urine; D008027:Light; D008099:Liver / Q000378:metabolism / Q000502:physiology*; D008297:Male; D009929:Organ Size / Q000502:physiology; D010084:Oxidation-Reduction; D010288:Parenteral Nutrition; D010477:Perfusion; D010777:Photochemistry; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D000596:Amino Acids; D008012:Lidocaine