Effect of genistein on the pharmacokinetics of paclitaxel administered orally or intravenously in rats

Li, Xiuguo; Choi, Jun‐Shik

doi:10.1016/j.ijpharm.2007.01.002

Cited by 73 publications

(39 citation statements)

References 27 publications

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“…It is also supported by the findings that quercetin, as a P-gp and CYP3A4 inhibitor, enhanced the oral bioavailability of paclitaxel [24] , and genistein, as a P-gp and CYP3A4 inhibitor, enhanced the oral bioavailability of paclitaxel administered orally or i.v. in rats [36] . In addition, cyclosporine A, another P-gp and CYP3A inhibitor, significantly increased the bioavailability of oral paclitaxel in humans [8] .…”

Section: Discussionmentioning

confidence: 98%

Effects of Silibinin, Inhibitor of CYP3A4 and P-Glycoprotein in vitro, on the Pharmacokinetics of Paclitaxel after Oral and Intravenous Administration in Rats

Lee

Choi

2010

Pharmacology

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Silibinin, a flavonoid, is an inhibitor of P-glycoprotein (P-gp)-mediated efflux transporters, and its oxidative metabolism is catalyzed by CYP3A4. The purpose of this study was to investigate the effect of oral silibinin on the bioavailability and pharmacokinetics of orally and intravenously administered paclitaxel in rats. The pharmacokinetic parameters of paclitaxel were determined in rats after oral (40 mg/kg) or intravenous (4 mg/kg) administration in the presence and absence of silibinin (0.5, 2.5 or 10 mg/kg). The effect of silibinin on the P-gp as well as CYP3A4 activity was also evaluated. Silibinin inhibited CYP3A4 enzyme activity with an IC₅₀ of 1.8 µmol/l. In addition, silibinin significantly inhibited P-gp activity. Compared to the control group, silibinin significantly (p < 0.05 by 2.5 mg/kg, p < 0.01 by 10 mg/kg) increased the area under the plasma concentration-time curve (65.8–101.7% higher) of oral paclitaxel. Silibinin also significantly increased (p < 0.05 by 2.5 mg/kg, 31.0% higher; p < 0.01 by 10 mg/kg, 52.9% higher) the peak plasma concentration of paclitaxel. Consequently, the absolute bioavailability of paclitaxel was increased by silibinin compared to that in the control group, and the relative bioavailability of oral paclitaxel was increased 1.15- to 2.02-fold. The intravenous pharmacokinetics of paclitaxel were not affected by the concurrent use of silibinin in contrast to the oral administration of paclitaxel. Accordingly, the enhanced oral bioavailability in the presence of silibinin could mainly be due to the increased intestinal absorption of paclitaxel via P-gp inhibition.

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Section: Discussionmentioning

confidence: 98%

Effects of Silibinin, Inhibitor of CYP3A4 and P-Glycoprotein in vitro, on the Pharmacokinetics of Paclitaxel after Oral and Intravenous Administration in Rats

Lee

Choi

2010

Pharmacology

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“…The inhibition of the efflux transporters by genistein also contributed the improvement of systemic exposure of paclitaxel [51] . The presence of genistein (10 mg/kg) caused an increase in AUC (54.7 % ) and a decrease in the total plasma clearance (35.2 % ) after oral administration of paclitaxel at a dose of 30 mg/kg in rats.…”

Section: Genisteinmentioning

confidence: 99%

Bioavailability enhancers of herbal origin: An overview

Kesarwani

Gupta

2013

Asian Pacific Journal of Tropical Biomedicine

362

197

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“…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).…”

Section: Abcb1 Inhibitors To Improve Taxane Oral Availabilitymentioning

confidence: 99%