A diclofenac suppository-nabumetone combination therapy for arthritic pain relief and a monitoring method for the diclofenac binding capacity of HSA site II in rheumatoid arthritis
ABSTRACT Diclofenac suppository, a non‐steroidal anti‐inflammatory drug (NSAID), is used widely in rheumatoid arthritis (RA) patients with severe arthritic pain. As the binding percentage of diclofenac to serum proteins is high, its free (unbound) concentration after rectal administration is low. To...
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| Veröffentlicht in: | Biopharmaceutics & drug disposition 2013-03, Vol.34 (2), p.125-136 |
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| creator | Setoguchi, Nao Takamura, Norito Fujita, Ken-ichi Ogata, Kenji Tokunaga, Jin Nishio, Toyotaka Chosa, Etsuo Arimori, Kazuhiko Kawai, Keiichi Yamamoto, Ryuichi |
| description | ABSTRACT
Diclofenac suppository, a non‐steroidal anti‐inflammatory drug (NSAID), is used widely in rheumatoid arthritis (RA) patients with severe arthritic pain. As the binding percentage of diclofenac to serum proteins is high, its free (unbound) concentration after rectal administration is low. To increase temporarily the free concentration of diclofenac and to enhance its analgesic effect by inhibiting the protein binding of diclofenac, the analgesic effect of diclofenac was examined before and after the start of an inhibitor administration to RA patients with insufficient control of arthritic pain, and the protein binding capacity of diclofenac was evaluated. Binding experiments were performed by ultrafiltration, and arthritic pain was recorded by the face scale. Free fractions of diazepam and diclofenac were augmented by increasing 6‐methoxy‐2‐naphthylacetic acid (6‐MNA; the active metabolite of the NSAID nabumetone) concentrations. The free fraction of diazepam increased after the start of nabumetone administration to RA patients, and arthritic pain relief was observed. These results suggest that 6‐MNA has an inhibitory effect on the protein binding of diclofenac and the free fraction of diazepam can be used to evaluate the binding capacity of diclofenac. It is considered that diclofenac suppository–nabumetone combination therapy and the method for protein binding monitoring by diazepam can positively benefit RA patients with insufficient control of arthritic pain. Copyright © 2013 John Wiley & Sons, Ltd. |
| doi_str_mv | 10.1002/bdd.1829 |
| format | Article |
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Diclofenac suppository, a non‐steroidal anti‐inflammatory drug (NSAID), is used widely in rheumatoid arthritis (RA) patients with severe arthritic pain. As the binding percentage of diclofenac to serum proteins is high, its free (unbound) concentration after rectal administration is low. To increase temporarily the free concentration of diclofenac and to enhance its analgesic effect by inhibiting the protein binding of diclofenac, the analgesic effect of diclofenac was examined before and after the start of an inhibitor administration to RA patients with insufficient control of arthritic pain, and the protein binding capacity of diclofenac was evaluated. Binding experiments were performed by ultrafiltration, and arthritic pain was recorded by the face scale. Free fractions of diazepam and diclofenac were augmented by increasing 6‐methoxy‐2‐naphthylacetic acid (6‐MNA; the active metabolite of the NSAID nabumetone) concentrations. The free fraction of diazepam increased after the start of nabumetone administration to RA patients, and arthritic pain relief was observed. These results suggest that 6‐MNA has an inhibitory effect on the protein binding of diclofenac and the free fraction of diazepam can be used to evaluate the binding capacity of diclofenac. It is considered that diclofenac suppository–nabumetone combination therapy and the method for protein binding monitoring by diazepam can positively benefit RA patients with insufficient control of arthritic pain. Copyright © 2013 John Wiley & Sons, Ltd.</description><identifier>ISSN: 0142-2782</identifier><identifier>EISSN: 1099-081X</identifier><identifier>DOI: 10.1002/bdd.1829</identifier><identifier>PMID: 23225308</identifier><identifier>CODEN: BDDID8</identifier><language>eng</language><publisher>Chichester: Blackwell Publishing Ltd</publisher><subject>Aged ; Arthritis, Rheumatoid - drug therapy ; Arthritis, Rheumatoid - metabolism ; Binding Sites ; Biological and medical sciences ; Butanones - administration & dosage ; Butanones - blood ; Butanones - pharmacokinetics ; Cyclooxygenase Inhibitors - administration & dosage ; Cyclooxygenase Inhibitors - blood ; Cyclooxygenase Inhibitors - pharmacokinetics ; diclofenac ; Diclofenac - administration & dosage ; Diclofenac - blood ; Diclofenac - pharmacokinetics ; Diseases of the osteoarticular system ; Drug Monitoring ; Drug Therapy, Combination ; Female ; human serum albumin ; Humans ; Inflammatory joint diseases ; Male ; Medical sciences ; Middle Aged ; nabumetone ; Pain - drug therapy ; Pain - metabolism ; Pharmacology. Drug treatments ; Protein Binding ; protein binding inhibition ; rheumatoid arthritis ; Serum Albumin - metabolism ; Suppositories</subject><ispartof>Biopharmaceutics & drug disposition, 2013-03, Vol.34 (2), p.125-136</ispartof><rights>Copyright © 2013 John Wiley & Sons, Ltd.</rights><rights>2014 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4589-4f2e8c3d18439f76866ed35dee925a0663b0c918309b3e850a55f9245c449e4c3</citedby><cites>FETCH-LOGICAL-c4589-4f2e8c3d18439f76866ed35dee925a0663b0c918309b3e850a55f9245c449e4c3</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%2Fbdd.1829$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fbdd.1829$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=27109662$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23225308$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Setoguchi, Nao</creatorcontrib><creatorcontrib>Takamura, Norito</creatorcontrib><creatorcontrib>Fujita, Ken-ichi</creatorcontrib><creatorcontrib>Ogata, Kenji</creatorcontrib><creatorcontrib>Tokunaga, Jin</creatorcontrib><creatorcontrib>Nishio, Toyotaka</creatorcontrib><creatorcontrib>Chosa, Etsuo</creatorcontrib><creatorcontrib>Arimori, Kazuhiko</creatorcontrib><creatorcontrib>Kawai, Keiichi</creatorcontrib><creatorcontrib>Yamamoto, Ryuichi</creatorcontrib><title>A diclofenac suppository-nabumetone combination therapy for arthritic pain relief and a monitoring method for the diclofenac binding capacity of HSA site II in rheumatoid arthritis</title><title>Biopharmaceutics & drug disposition</title><addtitle>Biopharm. Drug Dispos</addtitle><description>ABSTRACT
Diclofenac suppository, a non‐steroidal anti‐inflammatory drug (NSAID), is used widely in rheumatoid arthritis (RA) patients with severe arthritic pain. As the binding percentage of diclofenac to serum proteins is high, its free (unbound) concentration after rectal administration is low. To increase temporarily the free concentration of diclofenac and to enhance its analgesic effect by inhibiting the protein binding of diclofenac, the analgesic effect of diclofenac was examined before and after the start of an inhibitor administration to RA patients with insufficient control of arthritic pain, and the protein binding capacity of diclofenac was evaluated. Binding experiments were performed by ultrafiltration, and arthritic pain was recorded by the face scale. Free fractions of diazepam and diclofenac were augmented by increasing 6‐methoxy‐2‐naphthylacetic acid (6‐MNA; the active metabolite of the NSAID nabumetone) concentrations. The free fraction of diazepam increased after the start of nabumetone administration to RA patients, and arthritic pain relief was observed. These results suggest that 6‐MNA has an inhibitory effect on the protein binding of diclofenac and the free fraction of diazepam can be used to evaluate the binding capacity of diclofenac. It is considered that diclofenac suppository–nabumetone combination therapy and the method for protein binding monitoring by diazepam can positively benefit RA patients with insufficient control of arthritic pain. Copyright © 2013 John Wiley & Sons, Ltd.</description><subject>Aged</subject><subject>Arthritis, Rheumatoid - drug therapy</subject><subject>Arthritis, Rheumatoid - metabolism</subject><subject>Binding Sites</subject><subject>Biological and medical sciences</subject><subject>Butanones - administration & dosage</subject><subject>Butanones - blood</subject><subject>Butanones - pharmacokinetics</subject><subject>Cyclooxygenase Inhibitors - administration & dosage</subject><subject>Cyclooxygenase Inhibitors - blood</subject><subject>Cyclooxygenase Inhibitors - pharmacokinetics</subject><subject>diclofenac</subject><subject>Diclofenac - administration & dosage</subject><subject>Diclofenac - blood</subject><subject>Diclofenac - pharmacokinetics</subject><subject>Diseases of the osteoarticular system</subject><subject>Drug Monitoring</subject><subject>Drug Therapy, Combination</subject><subject>Female</subject><subject>human serum albumin</subject><subject>Humans</subject><subject>Inflammatory joint diseases</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>nabumetone</subject><subject>Pain - drug therapy</subject><subject>Pain - metabolism</subject><subject>Pharmacology. Drug treatments</subject><subject>Protein Binding</subject><subject>protein binding inhibition</subject><subject>rheumatoid arthritis</subject><subject>Serum Albumin - metabolism</subject><subject>Suppositories</subject><issn>0142-2782</issn><issn>1099-081X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1ks1u1DAURiMEokNB4gmQJYTEJsU_cRIvpy10BlVlAQjExnLsG8YlsVM7EeS9eEAcOkwREitvzj3flb-bZU8JPiEY01eNMSekpuJetiJYiBzX5PP9bIVJQXNa1fQoexTjNca4JIQ8zI4oo5QzXK-yn2tkrO58C05pFKdh8NGOPsy5U83Uw-gdIO37xjo1Wu_QuIOghhm1PiAVxl2wo9VoUNahAJ2FFilnkEK9d4vHuq8oWXbe_J5I03_nJatZCK0Gpe04I9-izfs1SisA2m7RIt3B1KvRW3OIi4-zB63qIjzZv8fZxzevP5xt8st3F9uz9WWuC16LvGgp1JoZUhdMtFVZlyUYxg2AoFzhsmQN1oLUDIuGQc2x4rwVtOC6KAQUmh1nL2-9Q_A3E8RR9jZq6DrlwE9REkY4YYxVLKHP_0Gv_RRc2m6hqkLw9PN3Qh18jAFaOQTbqzBLguXSpExNyqXJhD7bC6emB3MA_1SXgBd7QEWtujYop22846p0CWVJE5ffct9tB_N_A-Xp-fk-eM_bOMKPA6_CN1lWrOLy09WFpOL0S70pr-Rb9gv-2cUZ</recordid><startdate>201303</startdate><enddate>201303</enddate><creator>Setoguchi, Nao</creator><creator>Takamura, Norito</creator><creator>Fujita, Ken-ichi</creator><creator>Ogata, Kenji</creator><creator>Tokunaga, Jin</creator><creator>Nishio, Toyotaka</creator><creator>Chosa, Etsuo</creator><creator>Arimori, Kazuhiko</creator><creator>Kawai, Keiichi</creator><creator>Yamamoto, Ryuichi</creator><general>Blackwell Publishing Ltd</general><general>Wiley</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><scope>IQODW</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>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>201303</creationdate><title>A diclofenac suppository-nabumetone combination therapy for arthritic pain relief and a monitoring method for the diclofenac binding capacity of HSA site II in rheumatoid arthritis</title><author>Setoguchi, Nao ; Takamura, Norito ; Fujita, Ken-ichi ; Ogata, Kenji ; Tokunaga, Jin ; Nishio, Toyotaka ; Chosa, Etsuo ; Arimori, Kazuhiko ; Kawai, Keiichi ; Yamamoto, Ryuichi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4589-4f2e8c3d18439f76866ed35dee925a0663b0c918309b3e850a55f9245c449e4c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Aged</topic><topic>Arthritis, Rheumatoid - drug therapy</topic><topic>Arthritis, Rheumatoid - metabolism</topic><topic>Binding Sites</topic><topic>Biological and medical sciences</topic><topic>Butanones - administration & dosage</topic><topic>Butanones - blood</topic><topic>Butanones - pharmacokinetics</topic><topic>Cyclooxygenase Inhibitors - administration & dosage</topic><topic>Cyclooxygenase Inhibitors - blood</topic><topic>Cyclooxygenase Inhibitors - pharmacokinetics</topic><topic>diclofenac</topic><topic>Diclofenac - administration & dosage</topic><topic>Diclofenac - blood</topic><topic>Diclofenac - pharmacokinetics</topic><topic>Diseases of the osteoarticular system</topic><topic>Drug Monitoring</topic><topic>Drug Therapy, Combination</topic><topic>Female</topic><topic>human serum albumin</topic><topic>Humans</topic><topic>Inflammatory joint diseases</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>nabumetone</topic><topic>Pain - drug therapy</topic><topic>Pain - metabolism</topic><topic>Pharmacology. Drug treatments</topic><topic>Protein Binding</topic><topic>protein binding inhibition</topic><topic>rheumatoid arthritis</topic><topic>Serum Albumin - metabolism</topic><topic>Suppositories</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Setoguchi, Nao</creatorcontrib><creatorcontrib>Takamura, Norito</creatorcontrib><creatorcontrib>Fujita, Ken-ichi</creatorcontrib><creatorcontrib>Ogata, Kenji</creatorcontrib><creatorcontrib>Tokunaga, Jin</creatorcontrib><creatorcontrib>Nishio, Toyotaka</creatorcontrib><creatorcontrib>Chosa, Etsuo</creatorcontrib><creatorcontrib>Arimori, Kazuhiko</creatorcontrib><creatorcontrib>Kawai, Keiichi</creatorcontrib><creatorcontrib>Yamamoto, Ryuichi</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Biopharmaceutics & drug disposition</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Setoguchi, Nao</au><au>Takamura, Norito</au><au>Fujita, Ken-ichi</au><au>Ogata, Kenji</au><au>Tokunaga, Jin</au><au>Nishio, Toyotaka</au><au>Chosa, Etsuo</au><au>Arimori, Kazuhiko</au><au>Kawai, Keiichi</au><au>Yamamoto, Ryuichi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A diclofenac suppository-nabumetone combination therapy for arthritic pain relief and a monitoring method for the diclofenac binding capacity of HSA site II in rheumatoid arthritis</atitle><jtitle>Biopharmaceutics & drug disposition</jtitle><addtitle>Biopharm. Drug Dispos</addtitle><date>2013-03</date><risdate>2013</risdate><volume>34</volume><issue>2</issue><spage>125</spage><epage>136</epage><pages>125-136</pages><issn>0142-2782</issn><eissn>1099-081X</eissn><coden>BDDID8</coden><abstract>ABSTRACT
Diclofenac suppository, a non‐steroidal anti‐inflammatory drug (NSAID), is used widely in rheumatoid arthritis (RA) patients with severe arthritic pain. As the binding percentage of diclofenac to serum proteins is high, its free (unbound) concentration after rectal administration is low. To increase temporarily the free concentration of diclofenac and to enhance its analgesic effect by inhibiting the protein binding of diclofenac, the analgesic effect of diclofenac was examined before and after the start of an inhibitor administration to RA patients with insufficient control of arthritic pain, and the protein binding capacity of diclofenac was evaluated. Binding experiments were performed by ultrafiltration, and arthritic pain was recorded by the face scale. Free fractions of diazepam and diclofenac were augmented by increasing 6‐methoxy‐2‐naphthylacetic acid (6‐MNA; the active metabolite of the NSAID nabumetone) concentrations. The free fraction of diazepam increased after the start of nabumetone administration to RA patients, and arthritic pain relief was observed. These results suggest that 6‐MNA has an inhibitory effect on the protein binding of diclofenac and the free fraction of diazepam can be used to evaluate the binding capacity of diclofenac. It is considered that diclofenac suppository–nabumetone combination therapy and the method for protein binding monitoring by diazepam can positively benefit RA patients with insufficient control of arthritic pain. Copyright © 2013 John Wiley & Sons, Ltd.</abstract><cop>Chichester</cop><pub>Blackwell Publishing Ltd</pub><pmid>23225308</pmid><doi>10.1002/bdd.1829</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Aged Arthritis, Rheumatoid - drug therapy Arthritis, Rheumatoid - metabolism Binding Sites Biological and medical sciences Butanones - administration & dosage Butanones - blood Butanones - pharmacokinetics Cyclooxygenase Inhibitors - administration & dosage Cyclooxygenase Inhibitors - blood Cyclooxygenase Inhibitors - pharmacokinetics diclofenac Diclofenac - administration & dosage Diclofenac - blood Diclofenac - pharmacokinetics Diseases of the osteoarticular system Drug Monitoring Drug Therapy, Combination Female human serum albumin Humans Inflammatory joint diseases Male Medical sciences Middle Aged nabumetone Pain - drug therapy Pain - metabolism Pharmacology. Drug treatments Protein Binding protein binding inhibition rheumatoid arthritis Serum Albumin - metabolism Suppositories |
| title | A diclofenac suppository-nabumetone combination therapy for arthritic pain relief and a monitoring method for the diclofenac binding capacity of HSA site II in rheumatoid arthritis |
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