Presystemic metabolism of albendazole: Experimental evidence of an efflux process of albendazole sulfoxide to intestinal lumen

Albendazole (ABZ) presystemic clearance was studied in rat by perfusion of a 25 mu M ABZ solution in isolated intestinal loops. Significant secretion of the active metabolite, ABZSO, into the lumen was observed. The metabolit e was also present in mesenteric blood. After 30 min of intestinal perfusio n, 64% of the ABZ dose had disappeared from lumen. The total amount of ABZS O measured was 0.341 +/- 0.04 nmol/cm with 0.176 +/- 0.03 nmol/cm in mesent eric blood. The metabolite secretion to intestinal lumen was 0.165 +/- 0.05 nmol/cm. Intestinal sulfoxidation was induced by repeated administration o f ABZ and ABZ coadministered with surfactants, especially polysorbate 80. T he enantioselectivity of the in vitro intestinal sulfoxidation of ABZ showe d that the relative contribution of P-450 and flavin-containing monooxygena se was quite similar, but after the induction by ABZ coadministered with po lysorbate 80, the cytochrome P-450 system contribution was significantly in creased. The appearance of ABZSO in mesenteric blood clearance was also inc reased under these conditions.