Effects of silymarin and formulation on the oral bioavailability of paclitaxel in rats

Effects of lipid vehicle and P-glycoprotein inhibition on the mesenteric lymphatic transport of paclitaxel in unconscious, lymph duct-cannulated rats

“…Plasma concentration and oral bioavailability are prominently increased by pretreatment with verapamil, indicating that inhibition of P-gp markedly boosts the extent of PTX absorption via the portal blood. These results are consistent with the results reported by Choi & Li (2005), Woo et al (2003) and Park et al (2012). In these studies, P-gp inhibitors such as verapamil, verapamil analog KR30031 and silymarin were used to increase the bioavailability of PTX by inhibiting either the P-gp efflux pump or cytochrome P-450 (CYP3A).…”

“…blood concentration versus time data showed that the plasma AUC 0-8 h of PTX was 1008.61 ± 308.07 ng/h/mL, and clearance calculated as dose/ AUC was 521.40 ± 169.50 mL/h (n ¼ 3, mean ± SD). The mean(±SD) apparent biological half-life was 1.95 ± 1.07 h, which is comparable with that reported by Park et al (2012).…”

“…route-related adverse effects (Gao et al, 2003;Nornoo et al, 2009;Agueros et al, 2010). On the other hand, oral administration is hampered by the low bioavailability due to PTX's low solubility in water, cytochrome P-450 enzymes in the gut and liver, and high affinity to the multidrug efflux pump P-glycoprotein (P-gp) (Fisher & Sikic, 1995;Park et al, 2012).…”

Novel dietary lipid-based self-nanoemulsifying drug delivery systems of paclitaxel with p-gp inhibitor: implications on cytotoxicity and biopharmaceutical performance

“…Overall, the release studies revealed a net 3.24-fold improvement in the drug release rate for both the drugs from SNEDDS vis-a-vis the pure drug suspension. The obtained results were inconsonance with the literature reports confirming ability of SNEDDS for enhancing the dissolution performance of the poorly water soluble drugs including PTX and Cu, respectively [36,37].…”

Apical ABC Transporters and Cancer Chemotherapeutic Drug Disposition

“…The oral bioavailability of paclitaxel in rats is around 3.1-3.5%, but reported to be increased by coadministration of Schisandrol B ( Jin et al, 2010), naringin (up to 6.8%) (Choi & Shin, 2005), and flavones (up to 6.4%) (Choi, Choi, & Shin, 2004). Plasma exposure of paclitaxel in terms of AUC is also increased in rats after oral coadministration with genistein (Li & Choi, 2007), Biochanin A (Peng et al, 2006), 20(S)-Ginsenoside Rg3 (Yang et al, 2012), silymarin (Park, Park, Hur, Woo, & Lee, 2012), and its main component silibinin (Lee & Choi, 2010). Single oral coadministration of docetaxel with curcumin showed no effect on plasma exposure of docetaxel in rats, but pretreatment with curcumin for four consecutive days resulted in increased docetaxel absorption (Yan, Kim, Sung, Yong, & Choi, 2010).…”