Pharmacokinetic interaction potential assessment of cladrin, a potent bioactive constituent of Butea monosperma, and raloxifene, a prescription anti-osteoporotic by in vitro ADME approach

Abstract

Raloxifene is a well-known modulator of estrogen receptors which is structurally similar to tamoxifen. As flavonoids can interact with the estrogen modulator raloxifene in vitro, we performed an in vitro stability study and in situ permeability assay of raloxifene and cladrin in female Sprague-Dawley rats when administered alone and when co-administered. The in vitro study samples were analyzed by HPLC; raloxifene administered individually and in combination with cladrin was compared. In this study, we investigated the absorption, metabolic stability, plasma stability, determination of permeability and plasma protein binding of both drugs in SD rats using an established in situ single pass intestinal perfusion model. Increase in the bioavailability of raloxifene and cladrin alone or in co-administration also could be because of the activation of P-glycoprotein in the rat intestine. Further the present report concludes on the basis of ATPase assay of both raloxifene and cladrin alone and in combination showed that both drugs are P-gp substrate. In in situ permeability assay showed that the both drugs competitively lower the permeability of each other but still the predicted human permeability value lied in the range of high permeability drug.