Anthraquinone laxatives: metabolism and transport of danthron and rhein in the rat small and large intestine in vitro.

A previous in vitro study by Sund and Hillestad in 1982 showed that dihydroxy-diphenylmethane laxatives undergo intestinal metabolism, and suggested a regionally dependent transport asymmetry of gut glucuronides. The present study was initiated since such experiments on anthraquinone diphenols are lacking. Everted sacs of rat jejunum and stripped colon were filled with Krebs-Henseleit solution (K-H) on the serosal (BL) side, and bathed at the mucosal (LU) side with K-H containing either danthron (3-4 nmol/ml) or rhein (10 nmol/ml). After 60 min incubation at 37 degrees C, LU and BL solutions and gut tissue were analysed for parent diphenol and metabolites by reverse-phase high-pressure liquid chromatography. Reference metabolites were isolated and purified from urine and bile of rats infused with danthron or rhein. The studies showed: (1) only small amounts of unchanged drug were present on the contraluminal side; (2) in both tissues, danthron was transformed into its monoglucuronide (G) and monosulphate (S); the ratio G:S was 6-8:1 in jejunum, and even greater in colon; (3) in jejunum, G and S were mainly secreted (LU:BL distribution ratios greater than 10:1); (4) in the colon, however, the main G fraction was absorbed (BL:LU ratios of 3:1), whereas a slight net secretion of S seemed to take place; (5) residuals (%) in gut tissue were small; (6) rhein was more slowly taken up and metabolized, but seemed otherwise to behave as danthron. The results are in principle similar to those obtained by indirect conjugate assay in the study on diphenylmethanes.(ABSTRACT TRUNCATED AT 250 WORDS)