DMD Large equally mixed donor pool

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Rockich, K.
Right arrow Articles by Blouin, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rockich, K.
Right arrow Articles by Blouin, R.

Vol. 27, Issue 9, 1074-1077, September 1999

Effect of the Acute-Phase Response on the Pharmacokinetics of Chlorzoxazone and Cytochrome P-450 2E1 In Vitro Activity in Rats

Kevin Rockich1 and Robert Blouin1

Division of Pharmaceutical Sciences, University of Kentucky, College of Pharmacy, Lexington, Kentucky

The acute-phase response is known to produce alterations in hepatic cytochrome P-450 (CYP) expression. Lipopolysaccharide (LPS), a well known inducer of acute-phase response decreases hepatic CYP2E1 in vitro activity in rats. This study was designed to determine if LPS administration produced alterations in the pharmacokinetics of chlorzoxazone (CZN), a marker for CYP2E1 expression. Sprague-Dawley rats were administered a single i.p. injection of LPS (5 mg/kg) or saline control approximately 24 h before a single i.v. bolus dose of CZN (15 mg/kg). Serial blood samples were collected over a 120-min period to quantitate CZN plasma concentrations and protein binding. In addition, livers were removed and processed for evaluating in vitro CYP2E1 protein concentrations and activity. Systemic clearance decreased by 35% in LPS-treated rats, whereas half-life and steady-state volume of distribution increased by 167 and 66%, respectively. The plasma free-fraction of CZN increased 2-fold after LPS treatment. The CZN intrinsic clearance decreased in LPS rats by 71% compared with control values. The CYP2E1 liver microsomal activity decreased between 55 and 75% along with a 41% decrease in CYP2E1 protein concentration. The CZN intrinsic clearance was significantly correlated with both the CZN and p-nitrophenol liver microsomal activity (r = 0.97 and r = 0.91, respectively). This study demonstrated that LPS administration produced expected reductions in the in vivo intrinsic clearance of CZN, and these changes were highly correlated with in vitro activity studies. In addition, LPS produced significant increases in the steady-state volume of distribution of CZN secondary to reductions in its plasma protein binding.

1   Current address: University of Kentucky, College of Pharmacy, Division of Pharmaceutical Sciences, Lexington, KY 40536-0082.

Copyright © 1999 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 Drug Metab. Dispos.Home page
Y. Mu, M. M. Klamerus, T. M. Miller, L. C. Rohan, S. H. Graham, and S. M. Poloyac
Intravenous Formulation of N-Hydroxy-N'-(4-n-butyl-2-methylphenyl)formamidine (HET0016) for Inhibition of Rat Brain 20-Hydroxyeicosatetraenoic Acid Formation
Drug Metab. Dispos., November 1, 2008; 36(11): 2324 - 2330.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
C. Y. Ahn, S. K. Bae, Y. S. Jung, I. Lee, Y. C. Kim, M. G. Lee, and W. G. Shin
Pharmacokinetic Parameters of Chlorzoxazone and Its Main Metabolite, 6-Hydroxychlorzoxazone, after Intravenous and Oral Administration of Chlorzoxazone to Liver Cirrhotic Rats with Diabetes Mellitus
Drug Metab. Dispos., July 1, 2008; 36(7): 1233 - 1241.
[Abstract] [Full Text] [PDF]

Home page
 Innate ImmunityHome page
H.-N. Chen, S. Fan, and C.-F. Weng
Down-regulation of TGF{beta}1 and leptin ameliorates thioacetamide-induced liver injury in lipopolysaccharide-primed rats
Innate Immunity, June 1, 2007; 13(3): 176 - 188.
[Abstract] [PDF]

Home page
 Drug Metab. Dispos.Home page
S. M. Poloyac, M. A. Tortorici, D. I. Przychodzin, R. B. Reynolds, W. Xie, R. F. Frye, and M. A. Zemaitis
THE EFFECT OF ISONIAZID ON CYP2E1- AND CYP4A-MEDIATED HYDROXYLATION OF ARACHIDONIC ACID IN THE RAT LIVER AND KIDNEY
Drug Metab. Dispos., July 1, 2004; 32(7): 727 - 733.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
Y. J. Moon, A. K. Lee, H. C. Chung, E. J. Kim, S. H. Kim, D. C. Lee, I. Lee, S. G. Kim, and M. G. Lee
EFFECTS OF ACUTE RENAL FAILURE ON THE PHARMACOKINETICS OF CHLORZOXAZONE IN RATS
Drug Metab. Dispos., June 1, 2003; 31(6): 776 - 784.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
J. Hakkola, Y. Hu, and M. Ingelman-Sundberg
Mechanisms of Down-Regulation of CYP2E1 Expression by Inflammatory Cytokines in Rat Hepatoma Cells
J. Pharmacol. Exp. Ther., March 1, 2003; 304(3): 1048 - 1054.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
S. M. Poloyac, A. Perez, S. Scheff, and R. A. Blouin
Tissue-Specific Alterations in the 6-Hydroxylation of Chlorzoxazone Following Traumatic Brain Injury in the Rat
Drug Metab. Dispos., March 1, 2001; 29(3): 296 - 298.
[Abstract] [Full Text]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1999 by the American Society for Pharmacology and Experimental Therapeutics.