Abstract
Polyoxypregnanes (POPs) as novel P-glycoprotein (P-gp) modulators were derived from a Chinese medicinal herb, Marsdeniae Tenacissimae Caulis., which has long been used in combination anti-cancer therapy. Our previous study demonstrated that three most abundant POPs in the herb can reverse P-gp-mediated paclitaxel resistance. The objective of present study was to investigate potential pharmacokinetic (PK) interaction between paclitaxel and POPs in Sprague-Dawley (SD) rats. POPs were orally pretreated by 8 h before intravenous paclitaxel administration to jugular vein- and bile duct-cannulated male SD rats. Paclitaxel and its metabolites were analyzed with LC-MS in plasma, feces, urine, bile and different tissues. POPs significantly increased the area under plasma concentration-time curve of paclitaxel by 1.5 folds, without changing Cmax and elimination half-life of paclitaxel. POPs did not dramatically affect paclitaxel metabolism and tissue distribution profile. The excretions of the intact paclitaxel in the urine and bile were significantly decreased in the presence of POPs. These results indicated that enhanced systemic exposure of paclitaxel might be due to the inhibitory effects of POPs on the P-gp-mediated excretion of paclitaxel. Our study revealed minor PK interaction between paclitaxel and POPs, and provided basis for a potential therapeutic benefit of this combination therapy for cancer patients.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
