Title: Transport of artemisinin and sodium artesunate in Caco-2 intestinal epithelial cells
Authors: Augustijns, Patrick ×
D'Hulst, A
Van Daele, J
Kinget, Renaat #
Issue Date: Jun-1996
Series Title: Journal of pharmaceutical sciences vol:85 issue:6 pages:577-9
Abstract: Artemisinin and its derivatives are becoming interesting alternatives to the commonly used antimalarial drugs because they are efficient in treating severe and multidrug resistant forms of Plasmodium falciparum malaria. A major drawback is the occurrence of recrudescence some time after treatment. Moderate oral bioavailability has been suggested as a possible cause. As one of the factors that might limit absorption after oral administration, we studied the intestinal permeability using an in vitro system of the intestinal mucosa, Caco-2. Concentrations of artemisinin were determined by UV after alkaline degradation, while for sodium artesunate, a capillary electrophoresis method was developed. Artemisinin easily crossed the epithelial cells by passive diffusion (Papp = 30.4 +/- 1.7 x 10(-6) cm s-1, pH 7.4). Permeability of the hemisuccinate analogue, sodium artesunate, was 8-fold lower (Papp = 4.0 +/- 0.4 x 10(-6) cm s-1 at pH 7.4) and strongly dependent on pH, which might result in site dependent resorption in an in vivo situation. Enzyme catalyzed ester hydrolysis of sodium artesunate in Caco-2 monolayers to the biologically active metabolite, dihydroartemisinin, was moderate. The results indicate that the transepithelial permeability is probably not a limiting factor in the overall absorption process after oral administration of artemisinin or sodium artesunate. Solubility, dissolution rate, stability, and first-pass metabolism are suggested as alternative limiting factors.
ISSN: 0022-3549
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Drug Delivery and Disposition
× corresponding author
# (joint) last author

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