Min Han1, Xiao-Ling Fang. 1. Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 200032, China.
Abstract
AIM: To clarify the cause of poor oral absorption of ginsenoside Rg1 (Rg1), the active ingredient in Panax notoginseng saponins (PNS) used for treating hemorrhage. METHODS: Caco-2 cell monolayers were used as an in vitro model to study the transport mechanism of Rg1 across the intestinal mucosa. Moreover, the serum concentration-time profiles after peroral (po), intraduodenal (id), portal venous (pv) and tail venous (iv) administration of Rg1 in rats were compared to evaluate the first-pass effects in the stomach, intestine, and liver. RESULTS: Uptake of Rg1 by Caco-2 cell monolayers was temperature-dependent, but was not influenced by cyclosporin A. The change in the apical pH produced no obvious effect on the uptake of Rg1. The uptake and transport of Rg1 was non-saturable; whereas the flux from the apical compartment to the basolateral compartment (A-B) increased in a linear manner with the increase in concentration, indicating passive transport. An apparent permeability coefficient of (2.59+/-0.17)*10(-7) cm/s (C0=1 mg/mL) predicted incomplete absorption. A significant difference was observed between the po (F(po) was 3.29% at a dose of 1500 mg/kg), id (F(id) was 6.60% at a dose of 1200 mg/kg) and pv (F(pv) was 50.56%) administration methods, and the barrier function of the intestine was more significant than those of the stomach and liver in the absorption process. CONCLUSION: Elimination in the stomach, large intestine and liver contributed to the low oral bioavailability of Rg1, but low membrane permeability might be a more important factor in determining the extent of absorption.
AIM: To clarify the cause of poor oral absorption of ginsenosideRg1 (Rg1), the active ingredient in Panax notoginsengsaponins (PNS) used for treating hemorrhage. METHODS: Caco-2 cell monolayers were used as an in vitro model to study the transport mechanism of Rg1 across the intestinal mucosa. Moreover, the serum concentration-time profiles after peroral (po), intraduodenal (id), portal venous (pv) and tail venous (iv) administration of Rg1 in rats were compared to evaluate the first-pass effects in the stomach, intestine, and liver. RESULTS: Uptake of Rg1 by Caco-2 cell monolayers was temperature-dependent, but was not influenced by cyclosporin A. The change in the apical pH produced no obvious effect on the uptake of Rg1. The uptake and transport of Rg1 was non-saturable; whereas the flux from the apical compartment to the basolateral compartment (A-B) increased in a linear manner with the increase in concentration, indicating passive transport. An apparent permeability coefficient of (2.59+/-0.17)*10(-7) cm/s (C0=1 mg/mL) predicted incomplete absorption. A significant difference was observed between the po (F(po) was 3.29% at a dose of 1500 mg/kg), id (F(id) was 6.60% at a dose of 1200 mg/kg) and pv (F(pv) was 50.56%) administration methods, and the barrier function of the intestine was more significant than those of the stomach and liver in the absorption process. CONCLUSION: Elimination in the stomach, large intestine and liver contributed to the low oral bioavailability of Rg1, but low membrane permeability might be a more important factor in determining the extent of absorption.
Authors: Kar-Wah Leung; Hoi-Man Ng; Maggie K S Tang; Chris C K Wong; Ricky N S Wong; Alice S T Wong Journal: Angiogenesis Date: 2011-10-02 Impact factor: 9.596