Improved effectiveness of biochanin A as a P-gp inhibitor in solid dispersion.

The present study aimed to improve the in vivo effectiveness of biochanin A as a P-gp inhibitor by formulation in solid dispersion (SD). SDs were prepared with Solutol HS15 and hydroxypropylmethyl cellulose (HPMC2910) and their inhibition effect on P-gp mediated cellular efflux was examined by using NCI/ADR-RES cells overexpressing P-gp. Compared to the untreated biochanin A, SD formulations enhanced significantly (p < 0.01) the cellular uptake of rhodamine-123, a P-gp substrate by approximately 2-3 folds in NCI/ADR-RES cells. Furthermore, the oral and intravenous pharmacokinetics of diltiazem, a P-gp substrate as well as its active metabolite, desacetyldiltiazem, was determined in rats after pretreatment with biochanin A. Pretreatment with biochanin A in a SD formulation significantly (p < 0.05) increased the AUC of desacetyldiltiazem by 3-fold, although the oral exposure of diltiazem was not altered. In contrast, the intravenous pharmacokinetics of diltiazem and desacetyldiltiazem were not changed by the concurrent use of biochanin A, implying that oral biochanin A affected mainly the intestinal absorption of diltiazem rather than the hepatic extraction. In conclusion, SD formulation improved the in vivo effectiveness of biochanin A as a P-gp inhibitor.