Influence of albumin on enantioselective local disposition of BOF-4272, a xanthine oxidase inhibitor with chiral sulfoxide, in rat liver

Biological & Pharmaceutical Bulletin
M NishimuraT Nakagawa

Abstract

8-(3-Methoxy-4-phenylsulfinylphenyl) pyrazolo[1,5-a]-1,3,5-triazine-4(1H)-one (BOF-4272) blocks xanthine oxidase/xanthine dehydrogenase in the liver. BOF-4272 with a sulfoxide chiral center includes R(+)- and S(-)-enantiomers. The enantioselectivity in the global disposition of BOF-4272 can be attributed to that in the local disposition of organs, especially the liver. Thus, the enantioselectivity in the hepatic local disposition of BOF-4272 was compared between R- and S-enantiomers by a hepatic perfusion experiment with a pulse input into the portal vein. The influence of perfusate albumin on the enantioselective local disposition was also investigated. The elution time profile of each BOF-4272 enantiomer from the liver into the hepatic vein was measured at four different bovine serum albumin (BSA) concentrations (0, 0.25, 1.0 and 4.0%) in the perfusate at 37 and 4 degrees C. A crossover test was carried out for R- and S-enantiomers using one rat liver. In the absence of perfusate BSA at 37 degrees C, hepatic extraction ratios (E[H]) of R- and S-enantiomers of BOF-4272 were 75.6 +/- 4.3% and 71.7 +/- 3.3%, respectively, which were statistically the same. In the presence of 4.0% BSA at 37 degrees C, E(H) values of R- and S-enan...Continue Reading

Citations

Aug 12, 2014·European Journal of Medicinal Chemistry·Felicia Phei Lin Lim, Anton V Dolzhenko
May 30, 2002·Biological & Pharmaceutical Bulletin·Shinsaku Naito, Masuhiro Nishimura
Jan 5, 2002·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·S Naito, M Nishimura
May 20, 2020·Chemistry : a European Journal·Paola Acosta-GuzmánDiego Gamba-Sánchez

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