Document Detail


Pharmacokinetics of dicrofenac after its intrarectal and intracolostomal administration to rabbits with rectal resection or colostoma construction.
MedLine Citation:
PMID:  11745905     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We investigated the pharmacokinetics of diclofenac, one of the important analgesics in palliative care, after its intrarectal and intracolostomal administration to rabbits with rectal resection or colostoma construction. In rectal-resected rabbits, its bioavailability after rectal administration was significantly lower than that in normal rabbits, and furthermore that after intracolostomal administration was significantly lower than that in rectal-resected rabbits. This decreased bioavailability in rabbits with rectal resection and colostoma construction was thought to be due to the increased first-pass effect. With increase in the dose up to 1.5-fold, the plasma concentrations in both rectal-resected and colostoma-constructed rabbits increased to the normal rabbit level. These results indicate that the bioavailability of diclofenac sodium after its rectal and intracolostomal administration decreases, and that an increased dose can restore the decreased plasma concentration. There was no difference in the plasma concentration with diclofenac sodium suppositories between administration into the normal rectum and the remaining rectum following colostoma construction, and the remaining rectum was found to be a useful administration route for suppositories. Therefore, it was indicated that when administering diclofenac sodium suppositories to rectal-resected and colostoma-constructed patients, the dose should be increased, because the pharmacokinetics of diclofenac was similar in rabbits and human.
Authors:
K Nagasawa; H Nakanishi; T Matsuda; K Takara; N Ohnishi; T Yokoyama; S Fujimoto
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Biopharmaceutics & drug disposition     Volume:  22     ISSN:  0142-2782     ISO Abbreviation:  Biopharm Drug Dispos     Publication Date:  2001 Jan 
Date Detail:
Created Date:  2001-12-17     Completed Date:  2002-01-15     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  7911226     Medline TA:  Biopharm Drug Dispos     Country:  England    
Other Details:
Languages:  eng     Pagination:  31-9     Citation Subset:  IM    
Copyright Information:
Copyright 2001 John Wiley & Sons, Ltd.
Affiliation:
Department of Environmental Biochemistry, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan. nagasawa@mb.kyoto-phu.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Administration, Oral
Administration, Rectal
Animals
Anti-Inflammatory Agents, Non-Steroidal / administration & dosage,  blood,  pharmacokinetics*
Biological Availability
Colostomy*
Diclofenac / administration & dosage,  blood,  pharmacokinetics*
Injections, Intravenous
Male
Rabbits
Rectum / drug effects,  metabolism*,  surgery*
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents, Non-Steroidal; 15307-86-5/Diclofenac

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