Evaluation of P-glycoprotein modulation by pharmaceutical excipients

Abstract

Modulation of P-glycoprotein (P-gp) may play a significant role in the systemic delivery of poorly bioavailable drugs e.g. anti-neoplastic drugs. Many compounds from different chemical classes, including pharmaceutical excipients, have been proven to have inhibitory effects on P-gp mediated efflux transport, which leads to increased bioavailability. For the purpose of this study, different sub-classes of a group of excipients (i.e. disintegrants) were selected to evaluate the effect of ex vivo transport of a model compound across excised pig intestinal tissue. The model compound, namely Rhodamine 123 (R123), was selected on the basis that it is a known P-gp substrate. Results showed that certain of the selected disintegrants showed P-gp modulation but other disintegrants had no effect on R123 transport