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- Title
Pharmacokinetics of oltipraz in diabetic rats with liver cirrhosis.
- Authors
Ahn, C. Y.; Bae, S. K.; Bae, S. H.; Kim, T.; Jung, Y. S.; Kim, Y. C.; Lee, M. G.; Shin, W. G.
- Abstract
<bold>Background and Purpose: </bold>The incidence of diabetes mellitus is increased in patients with liver cirrhosis. Oltipraz is currently in trials to treat patients with liver fibrosis and cirrhosis induced by chronic hepatitis types B and C and is primarily metabolized via hepatic cytochrome P450 isozymes CYP1A1/2, 2B1/2, 2C11, 2D1 and 3A1/2 in rats. We have studied the influence of diabetes mellitus on pharmacokinetics of oltipraz and on expression of hepatic, CYP1A, 2B1/2, 2C11, 2D and 3A in rats with experimental liver cirrhosis.<bold>Experimental Approach: </bold>Oltipraz was given intravenously (10 mg x kg(-1)) or orally (30 mg x kg(-1)) to rats with liver cirrhosis induced by N-dimethylnitrosamine (LC rats) or with diabetes, induced by streptozotocin (DM rats) or to rats with both liver cirrhosis and diabetes (LCD rats) and to control rats, and pharmacokinetic variables measured. Protein expression of hepatic CYP1A, 2B1/2, 2C11, 2D and 3A was measured using Western blot analysis.<bold>Key Results: </bold>After i.v. or p.o. administration of oltipraz to LC and DM rats, the AUC was significantly greater and smaller, respectively, than that in control rats. In LCD rats, the AUC was that of LC and DM rats (partially restored towards control rats). Compared with control rats, the protein expression of hepatic CYP1A increased, that of CYP2C11 and 3A decreased, but that of CYP2B1/2 and 2D was not altered in LCD rats.<bold>Conclusions and Implications: </bold>In rats with diabetes and liver cirrhosis, the AUC of oltipraz was partially restored towards that of control rats.
- Subjects
PHARMACOKINETICS; DIABETES; LABORATORY rats; CIRRHOSIS of the liver; IMMUNOSUPPRESSIVE agents; DIABETES complications; SULFUR compounds; RESEARCH; HETEROCYCLIC compounds; ANIMAL experimentation; LIVER; RESEARCH methodology; MEDICAL cooperation; EVALUATION research; RATS; COMPARATIVE studies; ANTHELMINTICS; HEMOPROTEINS; DISEASE complications
- Publication
British Journal of Pharmacology, 2009, Vol 156, Issue 6, p1019
- ISSN
0007-1188
- Publication type
journal article
- DOI
10.1111/j.1476-5381.2008.00105.x