Linked Life Data

18619980

Source:http://linkedlifedata.com/resource/pubmed/id/18619980

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7-8
pubmed:dateCreated
2008-8-11
pubmed:abstractText
P-glycoprotein (P-gp) is found to play a very significant role in intestinal and biliary transport of irinotecan and its active metabolite, SN-38. This makes P-gp inhibition a logical strategy for improving irinotecan's oral efficacy and reducing its toxicity. The objective of the present study was to identify the most suitable P-gp inhibitor, amongst various commonly used herbal components via in vitro screening; followed by determination of in vivo effects in rats. Caco-2 cell monolayers were used to investigate the influence of various components (quercetin, hesperitin, piperine, curcumin and naringenin) on the transport of irinotecan. The secretory transport (basolateral-to-apical) was significantly decreased by all components (p<0.05) except piperine. In the apical-to-basolateral transport, quercetin showed the highest absorptive permeability enhancement and P-gp interaction potential making it an appropriate candidate for further in vivo studies in female Wistar rats. Quercetin pre-treatment resulted in increased irinotecan C(max) and area under curve (AUC) with a concomitant decrease in t(max), plasma clearance and volume of distribution (p<0.05). The absolute bioavailability (F) of irinotecan control was 33%, which was increased to 43% (1.3 fold) by quercetin administration. The amounts of irinotecan and SN-38 eliminated in bile in control rats, is reduced to almost half when treated with quercetin. Our studies not only propose a safe approach for bioavailability enhancement and reducing toxicity of irinotecan by P-gp inhibition but in another way also reiterate the significance of elucidating herb-drug interactions for future insights.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0024-3205
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
83
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
250-9
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Pre-clinical evidence for altered absorption and biliary excretion of irinotecan (CPT-11) in combination with quercetin: possible contribution of P-glycoprotein.
pubmed:affiliation
Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, Hamdard University, Hamdard Nagar, New Delhi 110062, India. dr.tripta@gmail.com
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't