Application of fractal kinetics for carrier-mediated transport of drugs across intestinal epithelial membrane.
OBJECTIVE
Fractal kinetics was used for the analysis of the carrier-mediated transport for drugs across the intestinal epithelial cells.


METHODS
The transport was examined under various agitation rates using a monolayer of Caco-2 cells and rabbit ileum sheets.


RESULTS
The passive transport of antipyrine across Caco-2 cells was increased with the increasing rate of agitation and was supposed to be caused by a change in the thickness of the unstirred water layer. On the contrary, in the case of L-lactic acid transport, which follows a carrier-mediated transport mechanism, the more the agitation rate controlling the fractal dimension was increased, the more the permeability rate across the Caco-2 cells was decreased. Fractal kinetic analysis of L-lactic acid transport indicated that the permeability was caused by a single saturable process. Similar agitation effects with L-lactic acid transport were observed in the transport of phenylalanine and cephradine in Caco-2 cells. However, the permeability rates of benzoic acid and 3-O-methyl-D-glucose across Caco-2 cells and L-lactic acid transport across the rabbit ileum tissue indicated the maximum levels at a designated agitation rate. This phenomenon was likely to be caused by the agitation effects controlling not only the fractal environment but also the unstirred water layer.


CONCLUSIONS
Carrier-mediated transports are well defined by fractal kinetics rather than classical kinetic analysis. Fractal kinetics are one of the important areas for understanding and confirming the properties of a carrier-mediated transport process.
Ogihara
T
T
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kanazawa University, Japan.
Tamai
I
I
Tsuji
A
A
D019325:3-O-Methylglucose / Q000378:metabolism; D000818:Animals; D000983:Antipyrine / Q000378:metabolism; D001565:Benzoates / Q000378:metabolism; D019817:Benzoic Acid; D001692:Biological Transport; D018938:Caco-2 Cells / Q000378:metabolism; D002463:Cell Membrane Permeability; D002515:Cephradine / Q000378:metabolism; D004058:Diffusion; D004848:Epithelium / Q000378:metabolism; D017709:Fractals; D006801:Humans; D007082:Ileum / Q000378:metabolism*; D007700:Kinetics; D019344:Lactic Acid / Q000378:metabolism; D008353:Mannitol / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010649:Phenylalanine / Q000378:metabolism; D011817:Rabbits
D001565:Benzoates; D004364:Pharmaceutical Preparations; D019325:3-O-Methylglucose; D019344:Lactic Acid; D008353:Mannitol; D010649:Phenylalanine; D019817:Benzoic Acid; D002515:Cephradine; D000983:Antipyrine