| Influence of albumin on enantioselective local disposition of BOF-4272, a xanthine oxidase inhibitor with chiral sulfoxide, in rat liver. | |
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MedLine Citation:
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PMID: 9448105 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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-enantiomers were 31.7 +/- 4.6% and 19.6 +/- 3.8%, respectively, which demonstrated that E(H) of R-enantiomer was significantly greater than that of S-enantiomer (p < 0.001). In the absence and presence of perfusate BSA at 4 degrees C, there was no significant difference in E(H) between S- and R-enantiomers. An amplification of stereoselectivity with albumin was observed by the perfusion experiment using BOF-4272 enantiomers. |
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Authors:
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M Nishimura; K Yamaoka; S Naito; T Nakagawa |
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Publication Detail:
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Type: In Vitro; Journal Article |
Journal Detail:
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Title: Biological & pharmaceutical bulletin Volume: 20 ISSN: 0918-6158 ISO Abbreviation: Biol. Pharm. Bull. Publication Date: 1997 Dec |
Date Detail:
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Created Date: 1998-03-16 Completed Date: 1998-03-16 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9311984 Medline TA: Biol Pharm Bull Country: JAPAN |
Other Details:
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Languages: eng Pagination: 1285-9 Citation Subset: IM |
Affiliation:
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Laboratory of Drug Metabolism Research, Naruto Research Institute, Otsuka Pharmaceutical Factory, Inc., Tokushima, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Albumins
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metabolism* Animals Enzyme Inhibitors / pharmacokinetics* Liver / metabolism* Male Protein Binding Rats Rats, Wistar Serum Albumin, Bovine / metabolism Spectrophotometry, Ultraviolet Stereoisomerism Sulfoxides / metabolism Triazines / pharmacokinetics* Xanthine Oxidase / antagonists & inhibitors* |
| Chemical | |
Reg. No./Substance:
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0/Albumins; 0/Enzyme Inhibitors; 0/Serum Albumin, Bovine; 0/Sulfoxides; 0/Triazines; 142181-44-0/BOF 4272; EC 1.17.3.2/Xanthine Oxidase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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