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. 2012 Jun;2(3):220-225.
doi: 10.1016/j.jpha.2012.01.007. Epub 2012 Jan 25.

Analysis of species-dependent hydrolysis and protein binding of esmolol enantiomers

Yi-Hong Tang  1   2 , Jun-Yan Wang  1 , Hai-Hong Hu  1 , Tong-Wei Yao  1 , Su Zeng  1
Affiliations

Analysis of species-dependent hydrolysis and protein binding of esmolol enantiomers

Yi-Hong Tang et al. J Pharm Anal. 2012 Jun.

Abstract

The stereoselective hydrolysis of esmolol in whole blood and in its separated components from rat, rabbit and human was investigated. Blood esterase activities were variable in different species in the order of rat>rabbit>human. Rat plasma showed the high esterase activity and had no stereoselectivity to enantiomers. Rabbit red blood cell (RBC) membrane, RBC cytosol and plasma all hydrolyzed esmolol but with different esterase activity, whereas the hydrolysis in RBC membrane and cytosol showed significant stereoselectivity towards R-(+)-esmolol. Esterase in RBC cytosol from human blood mainly contributed to the esmolol hydrolysis, which was demonstrated with no stereoselctivity. Esterase in human plasma showed a low activity, but a remarkable stereoselectivity with R-(+)-esmolol. In addition, the protein concentration affected the hydrolysis behavior of esmolol in RBC suspension. Protein binding of esmolol enantiomers in human plasma, human serum albumin (HSA) and α1-acid glycoprotein (AGP) revealed that there was a significant difference in bound fractions between two enantiomers, especially for AGP. Our results indicated that the stereoselective protein binding might play a role in the different hydrolysis rates of esmolol enantiomers in human plasma.

Keywords: Esmolol enantiomers; Protein binding; Species-dependent; Stereoselective hydrolysis.

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Figures

Figure 1
Figure 1
The binding of esmolol enantiomers to plasma proteins.
Figure 2
Figure 2
The binding of esmolol enantiomers to HSA. (A) The bound fraction of esmolol enantiomers vs. concentration in HSA; (B) the bound concentration vs. unbound concentration of esmolol enantiomers in HSA.
Figure 3
Figure 3
The binding of esmolol enantiomers to AGP. (A) The bound fraction of esmolol enantiomers vs. concentration in AGP; (B) scatchard plots for the binding of esmolol enantiomers in AGP.
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