Studies on the intestinal absorption characteristics of sulfasalazine, a breast cancer resistance protein (BCRP) substrate.

Oral sulfasalazine (SASP) is now used clinically as a probe substrate of a breast cancer resistance protein (BCRP) activity; however the intestinal absorption characteristics of SASP are not well understood. The purpose of this study was to clarify the characteristics of SASP transport in the mouse intestine. The everted ileum was incubated with SASP in the absence or presence of the Bcrp inhibitor Ko134. The steady-state intestinal absorptive clearance was 0.14 µL/min/cm in the absence of Ko134 and increased by 4.8-fold in the presence of Ko134. These results indicate that Bcrp mediates the efflux of SASP in the intestine. The absorptive clearance of SASP did not change in a concentration-dependent manner in the range of 0.1 to 50 µM in wild-type mice. By contrast, the absorptive clearance of SASP decreased significantly in a concentration-dependent manner in the presence of Ko134. Similar results were obtained in Bcrp(-/-) mice. These results suggest the possible involvement of some influx transporters in the intestinal absorption of SASP. In conclusion, both the influx and efflux transporters are involved in the intestinal absorption of SASP, which would explain why the absorptive clearance did not appear to change at various SASP concentrations in wild-type mice.