Enhanced oral bioavailability and anti-tumor effect of paclitaxel by 20(s)-Ginsenoside Rg3 in vivo.
Summary of "Enhanced oral bioavailability and anti-tumor effect of paclitaxel by 20(s)-Ginsenoside Rg3 in vivo."
The purpose of this study was to investigate the effect of paclitaxel in combination with 20(s)-Ginsenoside Rg3 on its anti-tumor effect in nude mice. In Caco-2 transport assay, P(app) (A-B) and P(app) (B-A) of paclitaxel were measured when co-incubation with different concentrations of 20(s)-Ginsenoside Rg3. Results indicated that the penetration of paclitaxel through the Caco-2 monolayer from the apical side to the basal side was facilitated by 20(s)-Ginsenoside Rg3 in a concentration-dependent manner. Meanwhile, 20(s)-Ginsenoside Rg3 inhibited P-gp, and the maximum inhibition was achieved at 80μM (P < 0.05). The pharmacokinetic parameters of paclitaxel after oral co-administration of paclitaxel (40 mg/kg) with various doses of 20(s)-Ginsenoside Rg3 in rats were investigated through in vivo pharmacokinetic experiment. The results showed that the AUC of paclitaxel co-administered with 20(s)-Ginsenoside Rg3 were significantly higher (P < 0.001 at 10 mg/kg) compared to the control. The RB % of paclitaxel with 20(s)-Ginsenoside Rg3 was 3.4-fold (10 mg/kg) higher than that of control. The effect of paclitaxel orally co-administered with 20(s)-Ginsenoside Rg3 against human tumor MCF-7 xenografts in nude mice was also evaluated. Paclitaxel (20mg/kg) co-administered with 20(s)-Ginsenoside Rg3 (10mg/kg) exhibited effective anti-tumor activity with T/C values of 39.36% (P <0.05). Our results showed that 20(s)-Ginsenoside Rg3 enhanced the oral bioavailability of paclitaxel in rats and improved the anti-tumor activity in nude mice, which indicated that orally co-administration paclitaxel with 20(s)-Ginsenoside Rg3 could provide an effective strategy in addition to the established IV route. Copyright © 2012 John Wiley & Sons, Ltd.
State Key Laboratory of Drug Metabolism, Hematological Pharmacology, Beijing Institute of Transfusion Medicine, 27 Taiping Road, Beijing, 100850, PR China; Laboratory of Cardiovascular Smooth Muscle, Shenyang Pharmaceutical University, 103 Wenhau Road, Sh
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Name: Biopharmaceutics & drug disposition
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