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Time-dependent changes in hepatic and intestinal induction of cytochrome P450 3A after administration of dexamethasone to rats.
MedLine Citation:
PMID:  23339625     Owner:  NLM     Status:  Publisher    
Abstract 1. We investigated the effects of the dose of and the number of times an inducer was administered and the duration of induction of hepatic and intestinal cytochrome P450 3A (CYP3A) in rats using dexamethasone 21-phosphate (DEX-P) and midazolam (MDZ) as an inducer and a substrate to CYP3A, respectively. 2. The number of times DEX-P was administered was not a significant factor in the induction of either hepatic or intestinal CYP3A; however, administration of DEX-P multiple times markedly decreased the bioavailability of DEX-P by self-induction of CYP3A. 3. CYP3A induction in the liver increased depending on the dose of DEX-P, whereas that in intestine showed a mild increase, but the induction level was almost constant regardless of the dose of DEX-P. 4. Administration of a single dose of DEX-P showed a temporal increase in CYP3A activity in both tissues and the induction ratios reached maximum values at 12 h after DEX-P administration. On the other hand, a mild increase of CYP3A activity, which lasted for at least 48 h, was observed in both tissues after administration of multiple doses. 5. Some physiological compounds such as cytokines might be involved in decreasing the CYP3A activity to maintain homeostasis of the body.
Kazunori Iwanaga; Tatsuya Honjo; Makoto Miyazaki; Masawo Kakemi
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-23
Journal Detail:
Title:  Xenobiotica; the fate of foreign compounds in biological systems     Volume:  -     ISSN:  1366-5928     ISO Abbreviation:  Xenobiotica     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1306665     Medline TA:  Xenobiotica     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Division of Pharmaceutics, Osaka University of Pharmaceutical Sciences , Nasahara, Takatsuki, Osaka , Japan.
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