High in situ rat intestinal permeability of artemisinin unaffected by multiple dosing and with no evidence of P-glycoprotein involvement
Language: 
English
Abstract: 

The objective of this study was to investigate whether the decrease in artemisinin bioavailability after repeated oral dosing in humans can be a result of increased efflux of artemisinin by P-glycoprotein or decreased membrane transport at the intestinal barrier. The effective jejunal permeability (Peff) of artemisinin was investigated using an in situ rat perfusion model. Fifty-four rats were randomized to one of three treatment arms: no pretreatment, pretreatment with artemisinin emulsion for 5 days (60 mg/kg/day, p.o. ), or pretreatment with emulsion vehicle for 5 days. The rats within each treatment arm were randomized further to be jejunally perfused with either low (500 ng/ml) or high (5000 ng/ml) artemisinin concentration or low artemisinin concentration plus the P-glycoprotein inhibitor R,S-verapamil (400 microg/ml). Perfusate samples were assayed for content of artemisinin, R,S-verapamil, and perfusion viability markers. Artemisinin Peff was 1.44 +/- 0.38, 1. 17 +/- 0.32, and 1.71 +/- 0.29 (.10(-4), cm/s) in rats receiving no pretreatment and perfused with low, high, or low artemisinin concentration plus verapamil, respectively. Multiple oral dosing of artemisinin did not affect the jejunal permeability of artemisinin. R,S-verapamil Peff was similar in artemisinin-pretreated rats (1.09 +/- 0.54. 10(-4), cm/s) and rats pretreated with only vehicle (1.07 +/- 0.37. 10(-4), cm/s). The decrease in artemisinin bioavailability after multiple oral dosing in human is probably not a result of changes in P-glycoprotein expression or general intestinal transport. It seems more likely attributed to increased hepatocellular activity. Furthermore, artemisinin exhibits high jejunal permeability and is neither a substrate nor inducer of P-glycoprotein.

Author(s): 
Svensson, U. S.
Sandström, R.
Carlborg, O.
Lennernäs, H.
Ashton, M.
Item Type: 
Journal Article
Publication Title: 
Drug Metabolism and Disposition: The Biological Fate of Chemicals
Journal Abbreviation: 
Drug Metab. Dispos.
Publication Date: 
Feb-99
Publication Year: 
1999
Pages: 
227-232
Volume: 
27
Issue: 
2
ISSN: 
0090-9556
Library Catalog: 
PubMed
Extra: 
PMID: 9929507

Turabian/Chicago Citation

U. S. Svensson, R. Sandström, O. Carlborg, H. Lennernäs and M. Ashton. Feb-99. "High in situ rat intestinal permeability of artemisinin unaffected by multiple dosing and with no evidence of P-glycoprotein involvement." Drug Metabolism and Disposition: The Biological Fate of Chemicals 27: 2: 227-232.

Wikipedia Citation

<ref> {{Cite journal | doi = | issn = 0090-9556 | volume = 27 | pages = 227-232 | last = Svensson | first = U. S. | coauthors = Sandström, R., Carlborg, O., Lennernäs, H., Ashton, M. | title = High in situ rat intestinal permeability of artemisinin unaffected by multiple dosing and with no evidence of P-glycoprotein involvement | journal = Drug Metabolism and Disposition: The Biological Fate of Chemicals | date = Feb-99 | pmid = | pmc = }} </ref>