Indican (indoxyl-β-D-glucoside), a precursor of the blue dyes indigo and indirubin, is abundant in the roots and leaves of Isatis indigotica L., a popular Chinese herb, which was increasingly used by the public during the SARS panic. This study aimed to investigate the pharmacokinetics of indican and furthermore, the effect of coadministration of indican on the absorption and disposition of methotrexate (MTX), a bicarboxylate antimetabolite with narrow therapeutic window, was evaluated.
Indican was orally administered to male Sprague-Dawley rats at doses of 20.0 and 40.0 mg/kg. The blood samples were withdrawn via cardiopunture and assayed by HPLC method for the concentrations of indican and indoxyl sulfate after deproteinization. Our results showed that indican was absorbed per se and mostly metabolized into indoxyl sulfate in rats.
Rats were orally given MTX with and without indican at doses of 10.0, 20.0 and 40.0 mg/kg in a parallel design. The blood concentrations of MTX were assayed by fluorescence polarization immunoassay (FPIA) method. Pharmacokinetic parameters were calculated using noncompartment model of WINNONLIN. The results study showed that coadministration of 20.0 and 40.0 mg/kg indican significantly increased the area under the curve (AUC0-t) and mean residence time (MRT) of MTX. In conclusion, indoxyl sulfate, a substrate of MRPs (multidrug resistance-associated proteins) and OATs (organic anion transporters), may compete MRPs/OATs with MTX to result in the delayed elimination of MTX. We suggested that for the sake of safety, the coadministration of indican-containing herbs with MTX should be avoided.
