Analgesic Effect of the Newly Developed S(+)-Flurbiprofen Plaster on Inflammatory Pain in a Rat Adjuvant-Induced Arthritis Model
ABSTRACT Preclinical Research This article describes the properties of a novel topical NSAID (Nonsteroidal anti‐inflammatory drug) patch, SFPP (S(+)‐flurbiprofen plaster), containing the potent cyclooxygenase (COX) inhibitor, S(+)‐flurbiprofen (SFP). The present studies were conducted to confirm hum...
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| creator | Sugimoto, Masanori Toda, Yoshihisa Hori, Miyuki Mitani, Akiko Ichihara, Takahiro Sekine, Shingo Hirose, Takuya Endo, Hiromi Futaki, Nobuko Kaku, Shinsuke Otsuka, Noboru Matsumoto, Hideo |
| description | ABSTRACT
Preclinical Research
This article describes the properties of a novel topical NSAID (Nonsteroidal anti‐inflammatory drug) patch, SFPP (S(+)‐flurbiprofen plaster), containing the potent cyclooxygenase (COX) inhibitor, S(+)‐flurbiprofen (SFP). The present studies were conducted to confirm human COX inhibition and absorption of SFP and to evaluate the analgesic efficacy of SFPP in a rat adjuvant‐induced arthritis (AIA) model. COX inhibition by SFP, ketoprofen and loxoprofen was evaluated using human recombinant COX proteins. Absorption of SFPP, ketoprofen and loxoprofen from patches through rat skin was assessed 24 h after application. The AIA model was induced by injecting Mycobacterium tuberculosis followed 20 days later by the evaluation of the prostaglandin PGE2 content of the inflamed paw and the pain threshold. SFP exhibited more potent inhibitory activity against COX‐1 (IC50 = 8.97 nM) and COX‐2 (IC50 = 2.94 nM) than the other NSAIDs evaluated. Absorption of SFP was 92.9%, greater than that of ketoprofen and loxoprofen from their respective patches. Application of SFPP decreased PGE2 content from 15 min to 6 h and reduced paw hyperalgesia compared with the control, ketoprofen and loxoprofen patches. SFPP showed analgesic efficacy, and was superior to the ketoprofen and loxoprofen patches, which could be through the potent COX inhibitory activity of SFP and greater skin absorption. The results suggested SFPP can be expected to exert analgesic effect clinically. Drug Dev Res 76 : 20–28, 2016. © 2016 Wiley Periodicals, Inc. |
| doi_str_mv | 10.1002/ddr.21288 |
| format | Article |
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Preclinical Research
This article describes the properties of a novel topical NSAID (Nonsteroidal anti‐inflammatory drug) patch, SFPP (S(+)‐flurbiprofen plaster), containing the potent cyclooxygenase (COX) inhibitor, S(+)‐flurbiprofen (SFP). The present studies were conducted to confirm human COX inhibition and absorption of SFP and to evaluate the analgesic efficacy of SFPP in a rat adjuvant‐induced arthritis (AIA) model. COX inhibition by SFP, ketoprofen and loxoprofen was evaluated using human recombinant COX proteins. Absorption of SFPP, ketoprofen and loxoprofen from patches through rat skin was assessed 24 h after application. The AIA model was induced by injecting Mycobacterium tuberculosis followed 20 days later by the evaluation of the prostaglandin PGE2 content of the inflamed paw and the pain threshold. SFP exhibited more potent inhibitory activity against COX‐1 (IC50 = 8.97 nM) and COX‐2 (IC50 = 2.94 nM) than the other NSAIDs evaluated. Absorption of SFP was 92.9%, greater than that of ketoprofen and loxoprofen from their respective patches. Application of SFPP decreased PGE2 content from 15 min to 6 h and reduced paw hyperalgesia compared with the control, ketoprofen and loxoprofen patches. SFPP showed analgesic efficacy, and was superior to the ketoprofen and loxoprofen patches, which could be through the potent COX inhibitory activity of SFP and greater skin absorption. The results suggested SFPP can be expected to exert analgesic effect clinically. Drug Dev Res 76 : 20–28, 2016. © 2016 Wiley Periodicals, Inc.</description><identifier>ISSN: 0272-4391</identifier><identifier>EISSN: 1098-2299</identifier><identifier>DOI: 10.1002/ddr.21288</identifier><identifier>PMID: 26763139</identifier><identifier>CODEN: DDREDK</identifier><language>eng</language><publisher>United States: Blackwell Publishing Ltd</publisher><subject>Administration, Topical ; analgesic ; Analgesics - administration & dosage ; Analgesics - pharmacokinetics ; Analgesics - pharmacology ; Animals ; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage ; Anti-Inflammatory Agents, Non-Steroidal - pharmacokinetics ; Anti-Inflammatory Agents, Non-Steroidal - pharmacology ; Arthritis, Experimental - drug therapy ; Arthritis, Experimental - immunology ; Cyclooxygenase 1 - metabolism ; Cyclooxygenase 2 - metabolism ; Cyclooxygenase Inhibitors - administration & dosage ; Cyclooxygenase Inhibitors - pharmacokinetics ; Cyclooxygenase Inhibitors - pharmacology ; Dinoprostone - metabolism ; Disease Models, Animal ; Flurbiprofen - administration & dosage ; Flurbiprofen - pharmacokinetics ; Flurbiprofen - pharmacology ; Humans ; Male ; nonsteroidal anti-inflammatory drugs ; Pain Threshold - drug effects ; Rats ; Rats, Sprague-Dawley ; S(+)-flurbiprofen</subject><ispartof>Drug development research, 2016-02, Vol.77 (1), p.20-28</ispartof><rights>2016 The Authors Drug Development Research Published by Wiley Periodicals, Inc.</rights><rights>2016 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5518-260e0eca627ee6f2736e7f8c019ca122ae8cc970fc1e9e1acd03c0db512be6233</citedby><cites>FETCH-LOGICAL-c5518-260e0eca627ee6f2736e7f8c019ca122ae8cc970fc1e9e1acd03c0db512be6233</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fddr.21288$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fddr.21288$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26763139$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sugimoto, Masanori</creatorcontrib><creatorcontrib>Toda, Yoshihisa</creatorcontrib><creatorcontrib>Hori, Miyuki</creatorcontrib><creatorcontrib>Mitani, Akiko</creatorcontrib><creatorcontrib>Ichihara, Takahiro</creatorcontrib><creatorcontrib>Sekine, Shingo</creatorcontrib><creatorcontrib>Hirose, Takuya</creatorcontrib><creatorcontrib>Endo, Hiromi</creatorcontrib><creatorcontrib>Futaki, Nobuko</creatorcontrib><creatorcontrib>Kaku, Shinsuke</creatorcontrib><creatorcontrib>Otsuka, Noboru</creatorcontrib><creatorcontrib>Matsumoto, Hideo</creatorcontrib><title>Analgesic Effect of the Newly Developed S(+)-Flurbiprofen Plaster on Inflammatory Pain in a Rat Adjuvant-Induced Arthritis Model</title><title>Drug development research</title><addtitle>Drug Dev. Res</addtitle><description>ABSTRACT
Preclinical Research
This article describes the properties of a novel topical NSAID (Nonsteroidal anti‐inflammatory drug) patch, SFPP (S(+)‐flurbiprofen plaster), containing the potent cyclooxygenase (COX) inhibitor, S(+)‐flurbiprofen (SFP). The present studies were conducted to confirm human COX inhibition and absorption of SFP and to evaluate the analgesic efficacy of SFPP in a rat adjuvant‐induced arthritis (AIA) model. COX inhibition by SFP, ketoprofen and loxoprofen was evaluated using human recombinant COX proteins. Absorption of SFPP, ketoprofen and loxoprofen from patches through rat skin was assessed 24 h after application. The AIA model was induced by injecting Mycobacterium tuberculosis followed 20 days later by the evaluation of the prostaglandin PGE2 content of the inflamed paw and the pain threshold. SFP exhibited more potent inhibitory activity against COX‐1 (IC50 = 8.97 nM) and COX‐2 (IC50 = 2.94 nM) than the other NSAIDs evaluated. Absorption of SFP was 92.9%, greater than that of ketoprofen and loxoprofen from their respective patches. Application of SFPP decreased PGE2 content from 15 min to 6 h and reduced paw hyperalgesia compared with the control, ketoprofen and loxoprofen patches. SFPP showed analgesic efficacy, and was superior to the ketoprofen and loxoprofen patches, which could be through the potent COX inhibitory activity of SFP and greater skin absorption. The results suggested SFPP can be expected to exert analgesic effect clinically. Drug Dev Res 76 : 20–28, 2016. © 2016 Wiley Periodicals, Inc.</description><subject>Administration, Topical</subject><subject>analgesic</subject><subject>Analgesics - administration & dosage</subject><subject>Analgesics - pharmacokinetics</subject><subject>Analgesics - pharmacology</subject><subject>Animals</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - administration & dosage</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - pharmacokinetics</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - pharmacology</subject><subject>Arthritis, Experimental - drug therapy</subject><subject>Arthritis, Experimental - immunology</subject><subject>Cyclooxygenase 1 - metabolism</subject><subject>Cyclooxygenase 2 - metabolism</subject><subject>Cyclooxygenase Inhibitors - administration & dosage</subject><subject>Cyclooxygenase Inhibitors - pharmacokinetics</subject><subject>Cyclooxygenase Inhibitors - pharmacology</subject><subject>Dinoprostone - metabolism</subject><subject>Disease Models, Animal</subject><subject>Flurbiprofen - administration & dosage</subject><subject>Flurbiprofen - pharmacokinetics</subject><subject>Flurbiprofen - pharmacology</subject><subject>Humans</subject><subject>Male</subject><subject>nonsteroidal anti-inflammatory drugs</subject><subject>Pain Threshold - drug effects</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>S(+)-flurbiprofen</subject><issn>0272-4391</issn><issn>1098-2299</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><recordid>eNp1kU1vEzEQhi0EoqFw4A8gS1yo0Lb-SOz1BSlK2hKRlioUwc1yvONmg7MOtjdtbv3pLKSN4IBkaQ5-5pmxX4ReU3JMCWEnVRWPGWVl-QT1KFFlwZhST1GPMMmKPlf0AL1IaUkIpf2yfI4OmJCCU6566H7YGH8Dqbb41DmwGQeH8wLwJdz6LR7DBnxYQ4W_vHt_VJz5Ns7rdQwOGnzlTcoQcWjwpHHerFYmh7jFV6ZucHcMnpmMh9Wy3ZgmF5Omam0nGsa8iHWuE74IFfiX6JkzPsGrh3qIvp6dXo8-FtPP55PRcFrYwYB2LxIECFgjmAQQjkkuQLrSEqqsoYwZKK1VkjhLQQE1tiLckmo-oGwOgnF-iD7svOt2voLKQpOj8Xod65WJWx1Mrf-9aeqFvgkb3S-pkpR1grcPghh-tpCyXoY2dr-XNJViwKlQQnXU0Y6yMaQUwe0nUKJ_h6W7sPSfsDr2zd8r7cnHdDrgZAfc1h62_zfp8Xj2qCx2HXUXzd2-w8QfWkguB_rb5bm--P5pOhuNpb7mvwDN3K8w</recordid><startdate>201602</startdate><enddate>201602</enddate><creator>Sugimoto, Masanori</creator><creator>Toda, Yoshihisa</creator><creator>Hori, Miyuki</creator><creator>Mitani, Akiko</creator><creator>Ichihara, Takahiro</creator><creator>Sekine, Shingo</creator><creator>Hirose, Takuya</creator><creator>Endo, Hiromi</creator><creator>Futaki, Nobuko</creator><creator>Kaku, Shinsuke</creator><creator>Otsuka, Noboru</creator><creator>Matsumoto, Hideo</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><general>John Wiley and Sons Inc</general><scope>BSCLL</scope><scope>24P</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope><scope>5PM</scope></search><sort><creationdate>201602</creationdate><title>Analgesic Effect of the Newly Developed S(+)-Flurbiprofen Plaster on Inflammatory Pain in a Rat Adjuvant-Induced Arthritis Model</title><author>Sugimoto, Masanori ; Toda, Yoshihisa ; Hori, Miyuki ; Mitani, Akiko ; Ichihara, Takahiro ; Sekine, Shingo ; Hirose, Takuya ; Endo, Hiromi ; Futaki, Nobuko ; Kaku, Shinsuke ; Otsuka, Noboru ; Matsumoto, Hideo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5518-260e0eca627ee6f2736e7f8c019ca122ae8cc970fc1e9e1acd03c0db512be6233</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Administration, Topical</topic><topic>analgesic</topic><topic>Analgesics - administration & dosage</topic><topic>Analgesics - pharmacokinetics</topic><topic>Analgesics - pharmacology</topic><topic>Animals</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - administration & dosage</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - pharmacokinetics</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - pharmacology</topic><topic>Arthritis, Experimental - drug therapy</topic><topic>Arthritis, Experimental - immunology</topic><topic>Cyclooxygenase 1 - metabolism</topic><topic>Cyclooxygenase 2 - metabolism</topic><topic>Cyclooxygenase Inhibitors - administration & dosage</topic><topic>Cyclooxygenase Inhibitors - pharmacokinetics</topic><topic>Cyclooxygenase Inhibitors - pharmacology</topic><topic>Dinoprostone - metabolism</topic><topic>Disease Models, Animal</topic><topic>Flurbiprofen - administration & dosage</topic><topic>Flurbiprofen - pharmacokinetics</topic><topic>Flurbiprofen - pharmacology</topic><topic>Humans</topic><topic>Male</topic><topic>nonsteroidal anti-inflammatory drugs</topic><topic>Pain Threshold - drug effects</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>S(+)-flurbiprofen</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sugimoto, Masanori</creatorcontrib><creatorcontrib>Toda, Yoshihisa</creatorcontrib><creatorcontrib>Hori, Miyuki</creatorcontrib><creatorcontrib>Mitani, Akiko</creatorcontrib><creatorcontrib>Ichihara, Takahiro</creatorcontrib><creatorcontrib>Sekine, Shingo</creatorcontrib><creatorcontrib>Hirose, Takuya</creatorcontrib><creatorcontrib>Endo, Hiromi</creatorcontrib><creatorcontrib>Futaki, Nobuko</creatorcontrib><creatorcontrib>Kaku, Shinsuke</creatorcontrib><creatorcontrib>Otsuka, Noboru</creatorcontrib><creatorcontrib>Matsumoto, Hideo</creatorcontrib><collection>Istex</collection><collection>Wiley Online Library Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Drug development research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sugimoto, Masanori</au><au>Toda, Yoshihisa</au><au>Hori, Miyuki</au><au>Mitani, Akiko</au><au>Ichihara, Takahiro</au><au>Sekine, Shingo</au><au>Hirose, Takuya</au><au>Endo, Hiromi</au><au>Futaki, Nobuko</au><au>Kaku, Shinsuke</au><au>Otsuka, Noboru</au><au>Matsumoto, Hideo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Analgesic Effect of the Newly Developed S(+)-Flurbiprofen Plaster on Inflammatory Pain in a Rat Adjuvant-Induced Arthritis Model</atitle><jtitle>Drug development research</jtitle><addtitle>Drug Dev. Res</addtitle><date>2016-02</date><risdate>2016</risdate><volume>77</volume><issue>1</issue><spage>20</spage><epage>28</epage><pages>20-28</pages><issn>0272-4391</issn><eissn>1098-2299</eissn><coden>DDREDK</coden><abstract>ABSTRACT
Preclinical Research
This article describes the properties of a novel topical NSAID (Nonsteroidal anti‐inflammatory drug) patch, SFPP (S(+)‐flurbiprofen plaster), containing the potent cyclooxygenase (COX) inhibitor, S(+)‐flurbiprofen (SFP). The present studies were conducted to confirm human COX inhibition and absorption of SFP and to evaluate the analgesic efficacy of SFPP in a rat adjuvant‐induced arthritis (AIA) model. COX inhibition by SFP, ketoprofen and loxoprofen was evaluated using human recombinant COX proteins. Absorption of SFPP, ketoprofen and loxoprofen from patches through rat skin was assessed 24 h after application. The AIA model was induced by injecting Mycobacterium tuberculosis followed 20 days later by the evaluation of the prostaglandin PGE2 content of the inflamed paw and the pain threshold. SFP exhibited more potent inhibitory activity against COX‐1 (IC50 = 8.97 nM) and COX‐2 (IC50 = 2.94 nM) than the other NSAIDs evaluated. Absorption of SFP was 92.9%, greater than that of ketoprofen and loxoprofen from their respective patches. Application of SFPP decreased PGE2 content from 15 min to 6 h and reduced paw hyperalgesia compared with the control, ketoprofen and loxoprofen patches. SFPP showed analgesic efficacy, and was superior to the ketoprofen and loxoprofen patches, which could be through the potent COX inhibitory activity of SFP and greater skin absorption. The results suggested SFPP can be expected to exert analgesic effect clinically. Drug Dev Res 76 : 20–28, 2016. © 2016 Wiley Periodicals, Inc.</abstract><cop>United States</cop><pub>Blackwell Publishing Ltd</pub><pmid>26763139</pmid><doi>10.1002/ddr.21288</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Administration, Topical analgesic Analgesics - administration & dosage Analgesics - pharmacokinetics Analgesics - pharmacology Animals Anti-Inflammatory Agents, Non-Steroidal - administration & dosage Anti-Inflammatory Agents, Non-Steroidal - pharmacokinetics Anti-Inflammatory Agents, Non-Steroidal - pharmacology Arthritis, Experimental - drug therapy Arthritis, Experimental - immunology Cyclooxygenase 1 - metabolism Cyclooxygenase 2 - metabolism Cyclooxygenase Inhibitors - administration & dosage Cyclooxygenase Inhibitors - pharmacokinetics Cyclooxygenase Inhibitors - pharmacology Dinoprostone - metabolism Disease Models, Animal Flurbiprofen - administration & dosage Flurbiprofen - pharmacokinetics Flurbiprofen - pharmacology Humans Male nonsteroidal anti-inflammatory drugs Pain Threshold - drug effects Rats Rats, Sprague-Dawley S(+)-flurbiprofen |
| title | Analgesic Effect of the Newly Developed S(+)-Flurbiprofen Plaster on Inflammatory Pain in a Rat Adjuvant-Induced Arthritis Model |
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