Planta Med 2006; 72(5): 398-404
DOI: 10.1055/s-2005-916211
Original Paper
Pharmacology
© Georg Thieme Verlag KG Stuttgart · New York

Oral Absorption of Ginsenoside Rb1 using in vitro and in vivo Models

Min Han1 , Xianyi Sha1 , Yunjuan Wu1 , Xiaoling Fang1
  • 1Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, P. R. China
Further Information

Publication History

Received: June 2, 2005

Accepted: October 1, 2005

Publication Date:
17 February 2006 (online)

Abstract

This research attempts to clarify the cause for poor oral absorption of ginsenoside Rb1 (Rb1), one main ingredient of the well known Panax notoginseng saponins (PNS) for curing hemorrhage. Caco-2 cell monolayers were used as an in vitro model to reveal the transport mechanism of Rb1 across the intestinal mucosa. Moreover, the serum concentration-time profiles of Rb1 after tail venous (IV), portal venous (PV), intraduodenal (ID) and peroral (PO) administration to rats were compared to evaluate the first-pass effects of stomach, intestine and liver. In vitro experiments showed that uptake by Caco-2 cell monolayers was temperature dependent, but was not influenced by cyclosporine A and ketoconazole. The change in the apical pH showed no obvious effects on the uptake of Rb1. The uptake and transport were non-saturable, and flux from the apical compartment to the basolateral compartment (A - B) increased linearly with increasing concentration, which indicated a passive transport. Meanwhile, an apparent permeability coefficient of (5.90 ± 1.02) × 10-8 cm/s (C0 = 1 mg/mL) predicted an incomplete absorption. The investigation on the pharmacokinetic behavior of Rb1 after different routes of administration to rats showed a significant difference between PO (FPO was 0.64 %), ID (FID was 2.46 %) and PV (FPV was 59.49 %) administration, and the first-pass effect of the intestine is more significant than that of the stomach and liver in the absorption process. In summary, elimination in the stomach, large intestine and liver contributed to the poor absorption of Rb1, but the low membrane permeability might be a more important factor dominating the extent of absorption.

Abbreviations

Rb1:ginsenoside Rb1

PNS:Panax notoginseng

A:apical

B:basolateral

HEPES:N-2-hydroxyethylpiperazine-N′-2-ethanesulfonic acid

MES:2-N-morpholineethanesulfonic acid

HBSS:Hanks balanced salt solution

CsA:cyclosporine A

KCZ:ketoconazole

Papp:apparent permeability coefficient

PO:peroral (administration)

ID:intraduodenal (administration)

PV:portal venous (administration)

IV:tail venous (administration)

FPO:absolute bioavailability after peroral administration

FID:absolute bioavailability after intraduodenal administration

FPV:absolute bioavailability after portal venous administration

FIV:absolute bioavailability after tail venous administration

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Xiaoling Fang

Department of Pharmaceutics

School of Pharmacy

Fudan University

138 Yixueyuan Road

Shanghai 200032

People’s Republic of China

Phone: +86-21-5423-7432

Fax: +86-21-5423-7432

Email: xlfang@shmu.edu.cn

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