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Sökning: WFRF:(Lennernas H)

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  • Berggren, S, et al. (författare)
  • Regional transport and metabolism of roivacaine and its CYP3A4 metabolite PPX in human intestine
  • 2003
  • Ingår i: Journal of Pharmacy and Pharmacology. - : Oxford University Press (OUP). - 0022-3573 .- 2042-7158. ; 55:7, s. 963-972
  • Tidskriftsartikel (refereegranskat)abstract
    • The major aim of this study was to investigate the CYP3A4 metabolism and polarized transport of ropivacaine and its metabolite 2',6'-pipecoloxylidide (PPX) in tissue specimens from the human small and large intestine. Ropivacaine has been shown to be effective in the treatment of ulcerative colitis in human colon. This study was conducted using a modified Ussing-chamber technique with specimens from jejunum, ileum and colon collected from 11 patients. The local kinetics of ropivacaine and PPX were assessed from their concentration-time profiles in mucosal and serosal compartments. The permeability (P-app) in the absorptive direction for both ropivacaine and PPX increased regionally in the order jejunum
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  • 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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