Abstract
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 ≈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.
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Abbreviations
- PN:
-
parenteral nutrition
- PN(-L):
-
light-protected PN group
- PN(+L):
-
light-exposed PN group
- CF:
-
chow-fed
- Cl int :
-
intrinsic clearance
- C in :
-
inlet concentration of lidocaine
- C out :
-
outlet concentration
- CYP:
-
cytochrome P450
- E H :
-
extraction ratio
- EMGX:
-
2-(N-ethyl-N-methylamino)-N-(2,6-dimethylphenyl)acetamide
- GX:
-
2-amino-N-(2, 6-dimethylphenyl)acetamide
- MVI:
-
multivitamin
- MEGX:
-
2-(ethylamino)-N-(2,6-dimethylphenyl)acetamide
- MeOH-MEGX:
-
2-(ethylamino)-N-(2-hydroxymethyl-6-methylphenyl)acetamide
- MeOH-lidocaine:
-
2-(diethylamino)-N-(2-hydroxymethyl-6-methylphenyl)acetamide
- 3-OH-lidocaine:
-
2-(diethylamino)-N-(2,6-dimethyl-3-hydroxyphenyl)acetamide
- 3-OH-MEGX:
-
2-(ethylamino)-N-(2,6-dimethyl-3-hydroxyphenyl)acetamide
- Q :
-
buffer perfusion rate
- RB:
-
riboflavin
- SB:
-
sodium bisulfite
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Zaman, N., Tam, Y., Jewell, L. et al. Effects of Light-Exposed Parenteral Nutrition on Hepatic Function and Lidocaine Metabolism: A Study Using Isolated Rat Liver Perfusion. Pediatr Res 40, 280–287 (1996). https://doi.org/10.1203/00006450-199608000-00015
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DOI: https://doi.org/10.1203/00006450-199608000-00015
