Preclinical factors affecting the pharmacokinetic behaviour of tanshinone IIA, an investigational new drug isolated from Salvia miltiorrhiza for the treatment of ischaemic heart diseases

Xenobiotica; the Fate of Foreign Compounds in Biological Systems
H-C BiMin Huang

Abstract

Tanshinone IIA (TSIIA) is a major active triterpenoid isolated from Salvia miltiorrhiza. The purposes of this study were to investigate various preclinical factors that determined the pharmacokinetics of TSIIA. After oral dosing at 6.7, 20, and 60 mg kg(-1), TSIIA was detected mainly as glucuronidated conjugate (TSIIAG) with only small amounts of the unchanged in the plasma. TSIIA was predominantly excreted into the bile and faeces as TSIIAG, and urine to a minor extent. The C(max) and AUC(0-)(t) of TSIIAG after i.p. administration were significantly lower than those after intragastric administration. The plasma concentration-time profiles of TSIIA following oral dosing of TSIIA showed multiple peaks. The C(max) and AUC(0-)(t) of TSIIA and its glucuronides in rats with intact bile duct were significantly lower than those of rats with bile duct cannulation. Studies from the linked-rat model and intraduodenal injection of bile containing TSIIA and its metabolites indicate that TSIIA glucuronides underwent hydrolysis and the aglycone was reabsorbed from the gut and excreted into the bile as conjugates. TSIIA had a wide tissue distribution, with a very high accumulation in the lung, but very limited penetration into the brain and t...Continue Reading

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Dec 4, 2012·International Journal of Molecular Sciences·Yong ZhangJunxuan Lü
Apr 16, 2011·International Journal of Biological Sciences·Xueying TanYanjie Lu
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Jan 29, 2019·Chemical & Pharmaceutical Bulletin·Jie LiangMing Yan
Feb 24, 2019·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Miao-Juan ShiHui Zhang

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