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Träfflista för sökning "WFRF:(LENNERNAS H) srt2:(1995-1999)"

Sökning: WFRF:(LENNERNAS H) > (1995-1999)

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1.
  • Svensson, Ulrika S H, et al. (författare)
  • High in situ rat intestinal permeability of artemisinin unaffected by multiple dosing and with no evidence of P-glycoprotein involvement
  • 1999
  • Ingår i: Drug Metabolism And Disposition. - 0090-9556 .- 1521-009X. ; 27:2, s. 227-232
  • Tidskriftsartikel (refereegranskat)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 (P-eff) 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 mu g/ml). Perfusate samples were assayed for content of artemisinin, R,S-verapamil, and perfusion viability markers. Artemisinin P-eff 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 P-eff 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.
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  • Lennernas, H (författare)
  • Human intestinal permeability
  • 1998
  • Ingår i: J PHARMACEUTICAL SCIENCES. ; 87, s. 403-
  • Tidskriftsartikel (refereegranskat)
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