Planta Med 2006; 72(14): 1311-1317
DOI: 10.1055/s-2006-951698
Original Paper
Pharmacology
© Georg Thieme Verlag KG Stuttgart · New York

Pharmacokinetics, Absorption and Tissue Distribution of Tanshinone IIA Solid Dispersion

Haiping Hao1 , Guangji Wang1 , Nan Cui1 , Jing Li1 , Lin Xie1 , Zuoqi Ding1
  • 1Key Lab of Drug Metabolism & Pharmacokinetics, China Pharmaceutical University, 1 Shennong Road, Nanjing, P. R. China
Further Information

Publication History

Received: July 6, 2006

Accepted: August 28, 2006

Publication Date:
06 October 2006 (online)

Abstract

This study was designed to elucidate the pharmacokinetics, absorption, tissue distribution and plasma protein binding properties of tanshinone IIA, a highly lipophilic compound isolated from Salvia miltiorrhiza. Tanshinone IIA was isolated using a previously well developed LC-MS/MS method. Its pharmacokinetic characteristics, absolute bioavailability, tissue distribution and plasma protein binding properties were determined. The membrane permeability was evaluated using Caco-2 cells in monolayer. The pharmacokinetic plasma profile of tanshinone IIA after a single intravenous dosing exhibited a triexponential pattern consisting of rapid distribution (t 1/2 α, 0.024 h), slow redistribution (t 1/2 β, 0.34 h) and terminal elimination phase (t 1/2 γ, 7.5 h). Tanshinone IIA preferentially distributed into the reticuloendothelial system, especially into liver and lung, after either intravenous or oral doses. Tanshinone IIA (99.2 %) bound highly to plasma proteins, among which lipoprotein played an important role (77.5 %). Tanshinone IIA absorption was extremely poor with an absolute bioavailability below 3.5 %. Absorptive saturation was deduced from the fact that the AUC and C max increased less proportionally to dose and t max was significantly prolonged. The poor absorption of tanshinone IIA may be caused by its low aqueous solubility and limited membrane permeability. There were no significant differences of the apparent permeability coefficient for all tested concentrations and for the apical to basolateral and reverse direction transport, suggesting a passive transport mode and no involvement of an efflux protein. In conclusion, tanshinone IIA has a suitable pharmacokinetic behavior except for its poor absorption. A pharmaceutical strategy for promoting its absorption should be designed to develop tanshinone IIA as a new drug candidate.

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Prof. Guangji Wang

Key Lab of Drug Metabolism & Pharmacokinetics E04#

China Pharmaceutical University

1 Shennong Road

Nanjing 210038

People’s Republic of China

Phone: +86-25-83271544

Fax: +86-25-85306750

Email: hhp_770505@yahoo.com.cn

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