The effect of the acute-phase response on in vitro drug metabolism and plasma protein binding in the horse

Mills, P. C., Ng, J. C. and Auer, D. E. (1997) The effect of the acute-phase response on in vitro drug metabolism and plasma protein binding in the horse. Veterinary Research Communications, 21 5: 361-368. doi:10.1023/A:1005816422279


Author Mills, P. C.
Ng, J. C.
Auer, D. E.
Title The effect of the acute-phase response on in vitro drug metabolism and plasma protein binding in the horse
Journal name Veterinary Research Communications   Check publisher's open access policy
ISSN 0165-7380
1573-7446
Publication date 1997-07-01
Year available 1997
Sub-type Article (original research)
DOI 10.1023/A:1005816422279
Open Access Status Not yet assessed
Volume 21
Issue 5
Start page 361
End page 368
Total pages 8
Place of publication Dordrecht, Netherlands
Publisher Springer
Language eng
Abstract The effect of the acute-phase response (APR) on the activity of the hepatic drug-metabolizing system (DMS) and on the binding of phenylbutazone to plasma proteins was investigated in the horse. An APR was induced by intramuscular injections of Freund's complete adjuvant in five horses and, five days later, these horses together with five clinically normal horses were shot and the right ventral lobe of each liver removed. The hepatic microsomal fractions from the liver samples were isolated and significantly lower (p<0.01) concentrations of cytochromes P450 and b(5) and activities of aniline-p-hydroxylase and aminopyrine N-demethylase (43%, 55%, 45% and 30%, respectively) were measured in the livers from the adjuvant-inflamed horses, compared to the controls. Phenylbutazone (PBZ) was administered intravenously (4.4 mg/kg) to a further four horses and plasma protein binding was measured by ultracentrifugation. Five weeks later, these horses were injected with Freund's complete adjuvant and the intravenous administration of PBZ (4.4 mg/kg) was repeated. Inflammation induced a significant increase (p<0.01) in the unbound fraction of PBZ (5.2 +/- 0.5 as against 1.4 +/- 0.6%). These results suggest that the APR depresses the hepatic DMS and reduces the binding of PBZ to plasma proteins.
Formatted abstract
The effect of the acute-phase response (APR) on the activity of the hepatic drug-metabolizing system (DMS) and on the binding of phenylbutazone to plasma proteins was investigated in the horse. An APR was induced by intramuscular injections of Freund's complete adjuvant in five horses and, five days later, these horses together with five clinically normal horses were shot and the right ventral lobe of each liver removed. The hepatic microsomal fractions from the liver samples were isolated and significantly lower (p<0.01) concentrations of cytochromes P450 and b(s) and activities of aniline-p-hydroxylase and aminopyrine N-demethylase (43%, 55%, 45% and 30%, respectively) were measured in the livers from the adjuvant-inflamed horses, compared to the controls. Phenylbutazone (PBZ) was administered intravenously (4.4 mg/kg) to a further four horses and plasma protein binding was measured by ultracentrifugation. Five weeks later, these horses were injected with Freund's complete adjuvant and the intravenous administration of PBZ (4.4 mg/kg) was repeated. Inflammation induced a significant increase (p<0.01) in the unbound fraction of PBZ (5.2±0.5 as against 1.4±0.6%). These results suggest that the APR depresses the hepatic DMS and reduces the binding of PBZ to plasma proteins.
Keyword Acute-phase response
Cytochrome
Enzyme
Horse
Inflammation
Liver
Microsome
Phenylbutazone
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: National Research Centre for Environmental Toxicology Publications
 
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