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Antimicrobial Agents and Chemotherapy, October 1998, p. 2607-2611, Vol. 42, No. 10
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Secretion of Sparfloxacin from the Human Intestinal Caco-2 Cell Line Is Altered by P-Glycoprotein Inhibitors

Estelle Cormet-Boyaka,1,dagger Jean-François Huneau,1,* Agnès Mordrelle,1 Prosper N. Boyaka,1,Dagger Claude Carbon,2 Ethan Rubinstein,3 and Daniel Tomé1

INRA, Unité de Nutrition Humaine et de Physiologie Intestinale, Institut National Agronomique Paris-Grignon, 75005 Paris,1 and Departement de Médecine Interne, INSERM U13, Hôpital Bichat, Paris,2 France, and Chaim Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel3

Received 2 December 1997/Returned for modification 7 April 1998/Accepted 28 July 1998

The mechanism of intestinal secretion of the difluorinated quinolone sparfloxacin was investigated with the epithelial cell line Caco-2 and was compared to that of the P-glycoprotein (P-gp) substrate vinblastine. The P-gp inhibitors verapamil and progesterone significantly increased the epithelial cell accumulation of both vinblastine and sparfloxacin. This increase is likely to result from an inhibition of drug secretion since both vinblastine uptake and sparfloxacin uptake are known to proceed through a passive transmembrane diffusion. The unidirectional fluxes across cell monlayers grown on permeable filters indicated that a net secretion of sparfloxacin and vinblastine occurred across Caco-2 cells. These secretions were significantly inhibited by the MDR-reversing agent verapamil. We conclude that the P-gp is likely to be involved in the intestinal elimination of the difluorinated quinolone sparfloxacin.

* Corresponding author. Mailing address: INRA, Unité de Nutrition Humaine et de Physiologie Intestinale, Institut National Agronomique Paris-Grignon, 16 rue Claude Bernard 75005 Paris, France. Phone: (33) 1-44.08.18.28. Fax: (33) 1-44.08.18.25. E-mail: huneau{at}rhin.inapg.inra.fr.

dagger Present address: UAB, BHS 985, Birmingham AL 35294-0005.

Dagger Present address: UAB, BBRB 762, Birmingham AL 35294-2170.

Antimicrobial Agents and Chemotherapy, October 1998, p. 2607-2611, Vol. 42, No. 10
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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