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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on September 27, 2005; DOI: 10.1124/jpet.105.090464

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*Compound via MeSH
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*Dietary Fats
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*TRIBUTYRIN


Received for publication June 24, 2005.
Revised September 12, 2005.
Accepted for publication September 16, 2005.

Evaluation of Tributyrin Lipid Emulsion with affinity to Low Density Lipoprotein: Pharmacokinetics in Adult Male Wistar Rats and Cellular Activity on Caco-2 and HepG2 Cell Lines

Jie Su 1, Li He 2, Ningning Zhang 1, Paul C. Ho 3*

1 National University of Singapore 2 The first Affliated Hospital of China Medical University 3 Department of Pharmacy

* Address correspondence to: E-mail: phahocl{at}nus.edu.sg

Abstract

The tributyrin lipid emulsion was proved able to bind to low-density lipoprotein (LDL) in vitro. The aim of this study was to investigate the pharmacokinetics of the emulsion in vivo and the cellular activity in vitro. The pharmacokinetics of tributyrin and its metabolite, butyrate was evaluated in male Wistar rats after administration with pure tributyrin or tributyrin emulsion. After oral administration, Cmax, Tmax and T1/2 of butyrate were 87.6 µM, 25.3 min and 63.0 min for the pure tributyrin compared to 1344.5 µM, 8.5 min and 19.8 min for the 10% (v/v) tributyrin emulsion. Cmax and MRT of tributyrin were 2.74 µM and 87.9 min, 4.2 µM and 132.0 min for pure tributyrin and 10% emulsion, respectively. The bioavailabilities of the pure tributyrin vs tributyrin emulsion were 15.3% vs 65.7% and 34.9% vs 64.5% calculated from butyrate and tributyrin, respectively. After the rats were treated with 17{alpha}-ethynylestradiol (a LDL receptor upregulator), the distribution volumes calculated from both butyrate and tributyrin were significantly increased after oral administration or infusion of the 10% tributyrin emulsion. The increased distribution volume after co-administration with a LDL receptor upregulator suggested the increased uptake of tributyrin/butyrate by tissues with increased expression of LDL receptors. The selective uptake of the emulsion by the cellular LDL receptors was further confirmed by testing the cellular viability in the presence of competing LDL. The viable cells can reach 92% of control at IC50 in Caco-2 and 77% in HepG2 incubated with emulsion in the presence of LDL.


Key words: butyric acid, emulsion, low density lipoprotein, pharmcokinetics, selective uptake, tributyrin


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