Metabolism and effect of para-toluene-sulfonamide on rat liver microsomal cytochrome P450 from in vivo and in vitro studies
Aim： To study the in vivo and in vitro metabolism and the effect of para-toluenesulfonamide （PTS） on cytochrome P450 enzymes （CYP450）. Methods： Total CYP450 and microsome protein content were determined after iv pretreatment of rats with PTS. CYP-specific substrates were incubated with rat liver mic...
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| Veröffentlicht in: | Acta pharmacologica Sinica 2006-05, Vol.27 (5), p.635-640 |
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| creator | ZHOU, Jiang‐quan TANG, Zhi‐qiang ZHANG, Jin‐nan TANG, Jing‐cheng |
| description | Aim： To study the in vivo and in vitro metabolism and the effect of para-toluenesulfonamide （PTS） on cytochrome P450 enzymes （CYP450）. Methods： Total CYP450 and microsome protein content were determined after iv pretreatment of rats with PTS. CYP-specific substrates were incubated with rat liver microsomes. Specific CYP isoform activities were determined by using HPLC. CYP chemical inhibitors added to the incubation mixture were used to investigate the principal CYP isoforms involved in PTS metabolism. The effect of PTS on CYP isoforms was investigated by incubating PTS with specific substrates. Results： The groups treated with 33 and 99 mg/kg per d PTS, respectively, had a total CYP content of 0.66±0.17 and 0.60±0.12 nmol/mg. The Km and Vmax were 92.2 μmol/L and 0.0137 nmol/min per mg protein. CYP2C7, CYP2D1 and CYP3A2 might contribute to PTS metabolism in the rat liver. The inhibitory effects of sulfaphenazole and ketoconazole on PTS metabolism were shown to have a mixed mechanism, whereas PTS metabolism was inhibited noncompetitively by quinidine. PTS had little effect on the activities of the selected CYP isoforms. Conclusion： Generally speaking, it is relatively safe for PTS to be co-administered with other drugs. However, care should be taken when administering PTS with CYP inhibitors and the substrates of CYP2C, CYP2D and CYP3A. |
| doi_str_mv | 10.1111/j.1745-7254.2006.00307.x |
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Methods： Total CYP450 and microsome protein content were determined after iv pretreatment of rats with PTS. CYP-specific substrates were incubated with rat liver microsomes. Specific CYP isoform activities were determined by using HPLC. CYP chemical inhibitors added to the incubation mixture were used to investigate the principal CYP isoforms involved in PTS metabolism. The effect of PTS on CYP isoforms was investigated by incubating PTS with specific substrates. Results： The groups treated with 33 and 99 mg/kg per d PTS, respectively, had a total CYP content of 0.66±0.17 and 0.60±0.12 nmol/mg. The Km and Vmax were 92.2 μmol/L and 0.0137 nmol/min per mg protein. CYP2C7, CYP2D1 and CYP3A2 might contribute to PTS metabolism in the rat liver. The inhibitory effects of sulfaphenazole and ketoconazole on PTS metabolism were shown to have a mixed mechanism, whereas PTS metabolism was inhibited noncompetitively by quinidine. PTS had little effect on the activities of the selected CYP isoforms. Conclusion： Generally speaking, it is relatively safe for PTS to be co-administered with other drugs. However, care should be taken when administering PTS with CYP inhibitors and the substrates of CYP2C, CYP2D and CYP3A.</description><identifier>ISSN: 1671-4083</identifier><identifier>EISSN: 1745-7254</identifier><identifier>DOI: 10.1111/j.1745-7254.2006.00307.x</identifier><identifier>PMID: 16626521</identifier><language>eng</language><publisher>Melbourne, Australia: Blackwell Publishing Asia</publisher><subject>Alcohol Oxidoreductases - metabolism ; Animals ; Anti-Infective Agents - pharmacology ; Aryl Hydrocarbon Hydroxylases - metabolism ; Cytochrome P-450 CYP3A ; Cytochrome P-450 Enzyme Inhibitors ; Cytochrome P-450 Enzyme System - metabolism ; cytochrome P450 ; Cytochrome P450 Family 2 ; HPLC ; inhibitor ; Ketoconazole - pharmacology ; liver microsomes ; Male ; Membrane Proteins - metabolism ; Microsomes, Liver - enzymology ; Microsomes, Liver - metabolism ; para‐toluene‐sulfonamide ; Rats ; Rats, Wistar ; Substrate Specificity ; Sulfaphenazole - pharmacology ; Sulfonamides - metabolism ; Sulfonamides - pharmacology ; Toluene - analogs & derivatives ; Toluene - metabolism ; Toluene - pharmacology ; 帕拉胶-甲苯-磺胺药物 ; 新陈代谢 ; 细胞色素P450 ; 肝疾病</subject><ispartof>Acta pharmacologica Sinica, 2006-05, Vol.27 (5), p.635-640</ispartof><rights>Copyright Nature Publishing Group May 2006</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4717-e46329e162b7d63657a383b139ee11a1ec0f94cbcd97c2bd91b4ba87f23d48783</citedby><cites>FETCH-LOGICAL-c4717-e46329e162b7d63657a383b139ee11a1ec0f94cbcd97c2bd91b4ba87f23d48783</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://image.cqvip.com/vip1000/qk/95561A/95561A.jpg</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1745-7254.2006.00307.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1745-7254.2006.00307.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27903,27904,45553,45554</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16626521$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>ZHOU, Jiang‐quan</creatorcontrib><creatorcontrib>TANG, Zhi‐qiang</creatorcontrib><creatorcontrib>ZHANG, Jin‐nan</creatorcontrib><creatorcontrib>TANG, Jing‐cheng</creatorcontrib><title>Metabolism and effect of para-toluene-sulfonamide on rat liver microsomal cytochrome P450 from in vivo and in vitro studies</title><title>Acta pharmacologica Sinica</title><addtitle>Acta Pharmacologica Sinica</addtitle><description>Aim： To study the in vivo and in vitro metabolism and the effect of para-toluenesulfonamide （PTS） on cytochrome P450 enzymes （CYP450）. Methods： Total CYP450 and microsome protein content were determined after iv pretreatment of rats with PTS. CYP-specific substrates were incubated with rat liver microsomes. Specific CYP isoform activities were determined by using HPLC. CYP chemical inhibitors added to the incubation mixture were used to investigate the principal CYP isoforms involved in PTS metabolism. The effect of PTS on CYP isoforms was investigated by incubating PTS with specific substrates. Results： The groups treated with 33 and 99 mg/kg per d PTS, respectively, had a total CYP content of 0.66±0.17 and 0.60±0.12 nmol/mg. The Km and Vmax were 92.2 μmol/L and 0.0137 nmol/min per mg protein. CYP2C7, CYP2D1 and CYP3A2 might contribute to PTS metabolism in the rat liver. The inhibitory effects of sulfaphenazole and ketoconazole on PTS metabolism were shown to have a mixed mechanism, whereas PTS metabolism was inhibited noncompetitively by quinidine. PTS had little effect on the activities of the selected CYP isoforms. Conclusion： Generally speaking, it is relatively safe for PTS to be co-administered with other drugs. However, care should be taken when administering PTS with CYP inhibitors and the substrates of CYP2C, CYP2D and CYP3A.</description><subject>Alcohol Oxidoreductases - metabolism</subject><subject>Animals</subject><subject>Anti-Infective Agents - pharmacology</subject><subject>Aryl Hydrocarbon Hydroxylases - metabolism</subject><subject>Cytochrome P-450 CYP3A</subject><subject>Cytochrome P-450 Enzyme Inhibitors</subject><subject>Cytochrome P-450 Enzyme System - metabolism</subject><subject>cytochrome P450</subject><subject>Cytochrome P450 Family 2</subject><subject>HPLC</subject><subject>inhibitor</subject><subject>Ketoconazole - pharmacology</subject><subject>liver microsomes</subject><subject>Male</subject><subject>Membrane Proteins - metabolism</subject><subject>Microsomes, Liver - enzymology</subject><subject>Microsomes, Liver - metabolism</subject><subject>para‐toluene‐sulfonamide</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Substrate Specificity</subject><subject>Sulfaphenazole - 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metabolism</topic><topic>Animals</topic><topic>Anti-Infective Agents - pharmacology</topic><topic>Aryl Hydrocarbon Hydroxylases - metabolism</topic><topic>Cytochrome P-450 CYP3A</topic><topic>Cytochrome P-450 Enzyme Inhibitors</topic><topic>Cytochrome P-450 Enzyme System - metabolism</topic><topic>cytochrome P450</topic><topic>Cytochrome P450 Family 2</topic><topic>HPLC</topic><topic>inhibitor</topic><topic>Ketoconazole - pharmacology</topic><topic>liver microsomes</topic><topic>Male</topic><topic>Membrane Proteins - metabolism</topic><topic>Microsomes, Liver - enzymology</topic><topic>Microsomes, Liver - metabolism</topic><topic>para‐toluene‐sulfonamide</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Substrate Specificity</topic><topic>Sulfaphenazole - pharmacology</topic><topic>Sulfonamides - metabolism</topic><topic>Sulfonamides - pharmacology</topic><topic>Toluene - analogs & derivatives</topic><topic>Toluene - metabolism</topic><topic>Toluene - pharmacology</topic><topic>帕拉胶-甲苯-磺胺药物</topic><topic>新陈代谢</topic><topic>细胞色素P450</topic><topic>肝疾病</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>ZHOU, Jiang‐quan</creatorcontrib><creatorcontrib>TANG, Zhi‐qiang</creatorcontrib><creatorcontrib>ZHANG, Jin‐nan</creatorcontrib><creatorcontrib>TANG, Jing‐cheng</creatorcontrib><collection>中文科技期刊数据库</collection><collection>中文科技期刊数据库-CALIS站点</collection><collection>中文科技期刊数据库-7.0平台</collection><collection>中文科技期刊数据库-医药卫生</collection><collection>中文科技期刊数据库- 镜像站点</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Acta pharmacologica Sinica</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>ZHOU, Jiang‐quan</au><au>TANG, Zhi‐qiang</au><au>ZHANG, Jin‐nan</au><au>TANG, Jing‐cheng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Metabolism and effect of para-toluene-sulfonamide on rat liver microsomal cytochrome P450 from in vivo and in vitro studies</atitle><jtitle>Acta pharmacologica Sinica</jtitle><addtitle>Acta Pharmacologica Sinica</addtitle><date>2006-05</date><risdate>2006</risdate><volume>27</volume><issue>5</issue><spage>635</spage><epage>640</epage><pages>635-640</pages><issn>1671-4083</issn><eissn>1745-7254</eissn><abstract>Aim： To study the in vivo and in vitro metabolism and the effect of para-toluenesulfonamide （PTS） on cytochrome P450 enzymes （CYP450）. Methods： Total CYP450 and microsome protein content were determined after iv pretreatment of rats with PTS. CYP-specific substrates were incubated with rat liver microsomes. Specific CYP isoform activities were determined by using HPLC. CYP chemical inhibitors added to the incubation mixture were used to investigate the principal CYP isoforms involved in PTS metabolism. The effect of PTS on CYP isoforms was investigated by incubating PTS with specific substrates. Results： The groups treated with 33 and 99 mg/kg per d PTS, respectively, had a total CYP content of 0.66±0.17 and 0.60±0.12 nmol/mg. The Km and Vmax were 92.2 μmol/L and 0.0137 nmol/min per mg protein. CYP2C7, CYP2D1 and CYP3A2 might contribute to PTS metabolism in the rat liver. The inhibitory effects of sulfaphenazole and ketoconazole on PTS metabolism were shown to have a mixed mechanism, whereas PTS metabolism was inhibited noncompetitively by quinidine. PTS had little effect on the activities of the selected CYP isoforms. Conclusion： Generally speaking, it is relatively safe for PTS to be co-administered with other drugs. However, care should be taken when administering PTS with CYP inhibitors and the substrates of CYP2C, CYP2D and CYP3A.</abstract><cop>Melbourne, Australia</cop><pub>Blackwell Publishing Asia</pub><pmid>16626521</pmid><doi>10.1111/j.1745-7254.2006.00307.x</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Alcohol Oxidoreductases - metabolism Animals Anti-Infective Agents - pharmacology Aryl Hydrocarbon Hydroxylases - metabolism Cytochrome P-450 CYP3A Cytochrome P-450 Enzyme Inhibitors Cytochrome P-450 Enzyme System - metabolism cytochrome P450 Cytochrome P450 Family 2 HPLC inhibitor Ketoconazole - pharmacology liver microsomes Male Membrane Proteins - metabolism Microsomes, Liver - enzymology Microsomes, Liver - metabolism para‐toluene‐sulfonamide Rats Rats, Wistar Substrate Specificity Sulfaphenazole - pharmacology Sulfonamides - metabolism Sulfonamides - pharmacology Toluene - analogs & derivatives Toluene - metabolism Toluene - pharmacology 帕拉胶-甲苯-磺胺药物 新陈代谢 细胞色素P450 肝疾病 |
| title | Metabolism and effect of para-toluene-sulfonamide on rat liver microsomal cytochrome P450 from in vivo and in vitro studies |
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