The prediction of the hepatic clearance of Tanshinone IIA in a rat liver subcellular fractions: accuracy improvement

Li, P., Wang, G-J., Li, J., Liu, X., Khlentzos, A. and Roberts, M. S. (2008) The prediction of the hepatic clearance of Tanshinone IIA in a rat liver subcellular fractions: accuracy improvement. Current Drug Metabolism, 9 1: 39-45. doi:10.2174/138920008783331103


Author Li, P.
Wang, G-J.
Li, J.
Liu, X.
Khlentzos, A.
Roberts, M. S.
Title The prediction of the hepatic clearance of Tanshinone IIA in a rat liver subcellular fractions: accuracy improvement
Journal name Current Drug Metabolism   Check publisher's open access policy
ISSN 1389-2002
Publication date 2008-01-01
Year available 2008
Sub-type Article (original research)
DOI 10.2174/138920008783331103
Open Access Status Not yet assessed
Volume 9
Issue 1
Start page 39
End page 45
Total pages 7
Editor C. Prakash
Place of publication The Netherlands
Publisher Bentham Science Publishers Ltd
Language eng
Subject C1
970111 Expanding Knowledge in the Medical and Health Sciences
111502 Clinical Pharmacology and Therapeutics
Abstract The in vivo hepatic clearance of tanshinone IIA in the rat was predicted using microsome, cytosol and S9 fractions combined with two different cofactor systems, NADPH-regenerating and UDPGA system. Two different models, the well stirred model and the parallel-tube model, were used in predicting the in vivo clearance in the rat. The in vivo clearance of tanshinone IIA was acquired from a pharmacokinetic study in rat. The results show that the prediction accuracy acquired from the microsome combined with the NADPH is poor. The in vivo clearance in the rat is almost 32 fold higher than the clearance predicted in microsome. The predicted clearance of the S9 model combined with both NADPH and UDPGA system is about 4 fold lower than the in vivo clearance. The predicted clearance of the cytosol combined with the two cofactor system is about 7 fold lower than the in vivo clearance. Although the prediction accuracy acquired from the S9 and cytosol system is not perfect, the prediction accuracy is improved in these two incubation systems. Using S9 combined with both the phase I and phase II metabolism can improve the prediction accuracy.
Keyword Biochemistry & Molecular Biology
Pharmacology & Pharmacy
Biochemistry & Molecular Biology
Pharmacology & Pharmacy
BIOCHEMISTRY & MOLECULAR BIOLOGY
PHARMACOLOGY & PHARMACY
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2009 Higher Education Research Data Collection
School of Medicine Publications
 
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Created: Wed, 01 Apr 2009, 06:30:23 EST by Maree Knight on behalf of School of Medicine