Minimal Effective Dose of Dysport and Botox in a Rat Model of Neurogenic Detrusor Overactivity
Abstract Background Two botulinum toxins A have been evaluated for the treatment of refractory neurogenic detrusor overactivity (NDO) in humans: Dysport (abobotulinumtoxinA) and Botox (onabotulinumtoxinA). However, these two distinct commercialized products have different potency units and are not i...
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| creator | Behr-Roussel, Delphine Oger, Stéphanie Pignol, Bernadette Pham, Emmanuel Le Maux, Amélie Chabrier, Pierre-Etienne Caisey, Stéphanie Compagnie, Sandrine Picaut, Philippe Bernabé, Jacques Alexandre, Laurent Giuliano, François Denys, Pierre |
| description | Abstract Background Two botulinum toxins A have been evaluated for the treatment of refractory neurogenic detrusor overactivity (NDO) in humans: Dysport (abobotulinumtoxinA) and Botox (onabotulinumtoxinA). However, these two distinct commercialized products have different potency units and are not interchangeable. Objective Assessment of the dose response and determination of minimal effective dose (MED) for Dysport and Botox in spinal cord–injured (SCI) rats with NDO. Design, setting, and participants Female, adult, Sprague-Dawley rats ( n = 98) underwent T8-T9 spinal cord transection. Nineteen days after spinal cord injury, rats received intradetrusor injections (25 μl injected, eight sites) of vehicle (V); Dysport 2, 5, 7.5, 10, and 12.5 U; and Botox 0.8, 2, 5, 7.5, and 10 U. Two days after injection, continuous cystometry was performed in conscious rats. Measurements Voiding contractions (VC) were assessed by duration of VC, intercontraction interval, voided volume, maximal pressure, pressure threshold change, and intravesical baseline pressure (BP), while nonvoiding contractions (NVC) were evaluated by amplitude, frequency, and volume threshold to elicit NVC. MEDs for Dysport and Botox were determined by analysis of variance step-down trend test. Results and limitations MEDs for Dysport and Botox were 10 U and 7.5 U, respectively. Regarding VC, only BP significantly decreased after 10 U Dysport and 7.5 U Botox compared to V (from 3.7 ± 0.6 to 1.5 ± 0.1 and 1.4 ± 0.3 mm Hg, respectively; p < 0.01 and p < 0.001, respectively). Dysport (10 U) and Botox (7.5 U) significantly inhibited NVC by decreasing their amplitude (from 7.4 ± 1.1 to 5.8 ± 0.5 and 5.4 ± 0.6 mm Hg, respectively; p < 0.05); frequency (from 2.2 ± 0.4 to 1.5 ± 0.2 and 1.3 ± 0.3 NVC per minute, respectively; p < 0.01); and increasing volume threshold to elicit NVC (from 29.8 ± 3.7 to 47.6 ± 6.9 and 47.7 ± 6.3%, respectively; p < 0.05 and p < 0.001, respectively). Conclusions This is the first preclinical dose-ranging study with Dysport and Botox under standardized conditions showing similar inhibiting effects on NDO, albeit at different MEDs. It highlights the importance of distinguishing each preparation for predicted outcomes and doses to be used. Further studies in patients with NDO are warranted to confirm these experimental results. |
| doi_str_mv | 10.1016/j.eururo.2012.01.051 |
| format | Article |
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However, these two distinct commercialized products have different potency units and are not interchangeable. Objective Assessment of the dose response and determination of minimal effective dose (MED) for Dysport and Botox in spinal cord–injured (SCI) rats with NDO. Design, setting, and participants Female, adult, Sprague-Dawley rats ( n = 98) underwent T8-T9 spinal cord transection. Nineteen days after spinal cord injury, rats received intradetrusor injections (25 μl injected, eight sites) of vehicle (V); Dysport 2, 5, 7.5, 10, and 12.5 U; and Botox 0.8, 2, 5, 7.5, and 10 U. Two days after injection, continuous cystometry was performed in conscious rats. Measurements Voiding contractions (VC) were assessed by duration of VC, intercontraction interval, voided volume, maximal pressure, pressure threshold change, and intravesical baseline pressure (BP), while nonvoiding contractions (NVC) were evaluated by amplitude, frequency, and volume threshold to elicit NVC. MEDs for Dysport and Botox were determined by analysis of variance step-down trend test. Results and limitations MEDs for Dysport and Botox were 10 U and 7.5 U, respectively. Regarding VC, only BP significantly decreased after 10 U Dysport and 7.5 U Botox compared to V (from 3.7 ± 0.6 to 1.5 ± 0.1 and 1.4 ± 0.3 mm Hg, respectively; p < 0.01 and p < 0.001, respectively). Dysport (10 U) and Botox (7.5 U) significantly inhibited NVC by decreasing their amplitude (from 7.4 ± 1.1 to 5.8 ± 0.5 and 5.4 ± 0.6 mm Hg, respectively; p < 0.05); frequency (from 2.2 ± 0.4 to 1.5 ± 0.2 and 1.3 ± 0.3 NVC per minute, respectively; p < 0.01); and increasing volume threshold to elicit NVC (from 29.8 ± 3.7 to 47.6 ± 6.9 and 47.7 ± 6.3%, respectively; p < 0.05 and p < 0.001, respectively). Conclusions This is the first preclinical dose-ranging study with Dysport and Botox under standardized conditions showing similar inhibiting effects on NDO, albeit at different MEDs. It highlights the importance of distinguishing each preparation for predicted outcomes and doses to be used. Further studies in patients with NDO are warranted to confirm these experimental results.]]></description><identifier>ISSN: 0302-2838</identifier><identifier>EISSN: 1873-7560</identifier><identifier>DOI: 10.1016/j.eururo.2012.01.051</identifier><identifier>PMID: 22341129</identifier><identifier>CODEN: EUURAV</identifier><language>eng</language><publisher>Kidlington: Elsevier B.V</publisher><subject>AbobotulinumtoxinA ; Animals ; Biological and medical sciences ; Botulinum Toxins, Type A - administration & dosage ; Cerebrospinal fluid. Meninges. Spinal cord ; Cystometry ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Experimental pharmacology ; Female ; Medical sciences ; Nephrology. Urinary tract diseases ; Nervous system (semeiology, syndromes) ; Neurology ; OnabotulinumtoxinA ; Rats ; Rats, Sprague-Dawley ; Spinal Cord Injuries - physiopathology ; Spinal cord injury ; Treatment Outcome ; Urinary Bladder, Neurogenic - drug therapy ; Urinary Bladder, Overactive - drug therapy ; Urinary system involvement in other diseases. Miscellaneous ; Urinary tract. Prostate gland ; Urination - drug effects ; Urination - physiology ; Urology</subject><ispartof>European urology, 2012-05, Vol.61 (5), p.1054-1061</ispartof><rights>European Association of Urology</rights><rights>2012 European Association of Urology</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c446t-ed2902431927f48b9abdb2f23e0760e5452f09dd6167bc84f23c1b8565296a993</citedby><cites>FETCH-LOGICAL-c446t-ed2902431927f48b9abdb2f23e0760e5452f09dd6167bc84f23c1b8565296a993</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.eururo.2012.01.051$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,777,781,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25768066$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22341129$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Behr-Roussel, Delphine</creatorcontrib><creatorcontrib>Oger, Stéphanie</creatorcontrib><creatorcontrib>Pignol, Bernadette</creatorcontrib><creatorcontrib>Pham, Emmanuel</creatorcontrib><creatorcontrib>Le Maux, Amélie</creatorcontrib><creatorcontrib>Chabrier, Pierre-Etienne</creatorcontrib><creatorcontrib>Caisey, Stéphanie</creatorcontrib><creatorcontrib>Compagnie, Sandrine</creatorcontrib><creatorcontrib>Picaut, Philippe</creatorcontrib><creatorcontrib>Bernabé, Jacques</creatorcontrib><creatorcontrib>Alexandre, Laurent</creatorcontrib><creatorcontrib>Giuliano, François</creatorcontrib><creatorcontrib>Denys, Pierre</creatorcontrib><title>Minimal Effective Dose of Dysport and Botox in a Rat Model of Neurogenic Detrusor Overactivity</title><title>European urology</title><addtitle>Eur Urol</addtitle><description><![CDATA[Abstract Background Two botulinum toxins A have been evaluated for the treatment of refractory neurogenic detrusor overactivity (NDO) in humans: Dysport (abobotulinumtoxinA) and Botox (onabotulinumtoxinA). However, these two distinct commercialized products have different potency units and are not interchangeable. Objective Assessment of the dose response and determination of minimal effective dose (MED) for Dysport and Botox in spinal cord–injured (SCI) rats with NDO. Design, setting, and participants Female, adult, Sprague-Dawley rats ( n = 98) underwent T8-T9 spinal cord transection. Nineteen days after spinal cord injury, rats received intradetrusor injections (25 μl injected, eight sites) of vehicle (V); Dysport 2, 5, 7.5, 10, and 12.5 U; and Botox 0.8, 2, 5, 7.5, and 10 U. Two days after injection, continuous cystometry was performed in conscious rats. Measurements Voiding contractions (VC) were assessed by duration of VC, intercontraction interval, voided volume, maximal pressure, pressure threshold change, and intravesical baseline pressure (BP), while nonvoiding contractions (NVC) were evaluated by amplitude, frequency, and volume threshold to elicit NVC. MEDs for Dysport and Botox were determined by analysis of variance step-down trend test. Results and limitations MEDs for Dysport and Botox were 10 U and 7.5 U, respectively. Regarding VC, only BP significantly decreased after 10 U Dysport and 7.5 U Botox compared to V (from 3.7 ± 0.6 to 1.5 ± 0.1 and 1.4 ± 0.3 mm Hg, respectively; p < 0.01 and p < 0.001, respectively). Dysport (10 U) and Botox (7.5 U) significantly inhibited NVC by decreasing their amplitude (from 7.4 ± 1.1 to 5.8 ± 0.5 and 5.4 ± 0.6 mm Hg, respectively; p < 0.05); frequency (from 2.2 ± 0.4 to 1.5 ± 0.2 and 1.3 ± 0.3 NVC per minute, respectively; p < 0.01); and increasing volume threshold to elicit NVC (from 29.8 ± 3.7 to 47.6 ± 6.9 and 47.7 ± 6.3%, respectively; p < 0.05 and p < 0.001, respectively). Conclusions This is the first preclinical dose-ranging study with Dysport and Botox under standardized conditions showing similar inhibiting effects on NDO, albeit at different MEDs. It highlights the importance of distinguishing each preparation for predicted outcomes and doses to be used. Further studies in patients with NDO are warranted to confirm these experimental results.]]></description><subject>AbobotulinumtoxinA</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Botulinum Toxins, Type A - administration & dosage</subject><subject>Cerebrospinal fluid. Meninges. Spinal cord</subject><subject>Cystometry</subject><subject>Disease Models, Animal</subject><subject>Dose-Response Relationship, Drug</subject><subject>Experimental pharmacology</subject><subject>Female</subject><subject>Medical sciences</subject><subject>Nephrology. Urinary tract diseases</subject><subject>Nervous system (semeiology, syndromes)</subject><subject>Neurology</subject><subject>OnabotulinumtoxinA</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Spinal Cord Injuries - physiopathology</subject><subject>Spinal cord injury</subject><subject>Treatment Outcome</subject><subject>Urinary Bladder, Neurogenic - drug therapy</subject><subject>Urinary Bladder, Overactive - drug therapy</subject><subject>Urinary system involvement in other diseases. Miscellaneous</subject><subject>Urinary tract. Prostate gland</subject><subject>Urination - drug effects</subject><subject>Urination - physiology</subject><subject>Urology</subject><issn>0302-2838</issn><issn>1873-7560</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkk1v1DAQhi0EokvhHyDkC-KUMP6IE1-QoNsWpJZKfFyxHGeCvGTjrZ2s2H-Po11A4sLJBz_zzuiZIeQ5g5IBU683Jc5xjqHkwHgJrISKPSAr1tSiqCsFD8kKBPCCN6I5I09S2gCAqLR4TM44F5Ixrlfk260f_dYO9LLv0U1-j3QdEtLQ0_Uh7UKcqB07-i5M4Sf1I7X0k53obehwWJiPeYbwHUfv6BqnOKcQ6d0eo12i_HR4Sh71dkj47PSek69Xl18u3hc3d9cfLt7eFE5KNRXYcQ1cCqZ53cum1bbtWt5zgVArwEpWvAfddYqpunWNzD-OtU2lKq6V1Vqck1fH3F0M9zOmyWx9cjgMdsQwJ6OV5ABS80zKI-liSClib3YxC4gHw8AsYs3GHMWaRawBZrLYXPbi1GBut9j9KfptMgMvT4BNzg59tKPz6S9X1aoBpTL35shh1rH3GE1yHkeHnY95AaYL_n-T_BvghrzD3PMHHjBtwhzHrNowk3KN-bwcwXIDLAtgSjfiF7qArEc</recordid><startdate>20120501</startdate><enddate>20120501</enddate><creator>Behr-Roussel, Delphine</creator><creator>Oger, Stéphanie</creator><creator>Pignol, Bernadette</creator><creator>Pham, Emmanuel</creator><creator>Le Maux, Amélie</creator><creator>Chabrier, Pierre-Etienne</creator><creator>Caisey, Stéphanie</creator><creator>Compagnie, Sandrine</creator><creator>Picaut, Philippe</creator><creator>Bernabé, Jacques</creator><creator>Alexandre, Laurent</creator><creator>Giuliano, François</creator><creator>Denys, Pierre</creator><general>Elsevier B.V</general><general>Elsevier</general><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>7X8</scope></search><sort><creationdate>20120501</creationdate><title>Minimal Effective Dose of Dysport and Botox in a Rat Model of Neurogenic Detrusor Overactivity</title><author>Behr-Roussel, Delphine ; Oger, Stéphanie ; Pignol, Bernadette ; Pham, Emmanuel ; Le Maux, Amélie ; Chabrier, Pierre-Etienne ; Caisey, Stéphanie ; Compagnie, Sandrine ; Picaut, Philippe ; Bernabé, Jacques ; Alexandre, Laurent ; Giuliano, François ; Denys, Pierre</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c446t-ed2902431927f48b9abdb2f23e0760e5452f09dd6167bc84f23c1b8565296a993</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>AbobotulinumtoxinA</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Botulinum Toxins, Type A - administration & dosage</topic><topic>Cerebrospinal fluid. Meninges. Spinal cord</topic><topic>Cystometry</topic><topic>Disease Models, Animal</topic><topic>Dose-Response Relationship, Drug</topic><topic>Experimental pharmacology</topic><topic>Female</topic><topic>Medical sciences</topic><topic>Nephrology. Urinary tract diseases</topic><topic>Nervous system (semeiology, syndromes)</topic><topic>Neurology</topic><topic>OnabotulinumtoxinA</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Spinal Cord Injuries - physiopathology</topic><topic>Spinal cord injury</topic><topic>Treatment Outcome</topic><topic>Urinary Bladder, Neurogenic - drug therapy</topic><topic>Urinary Bladder, Overactive - drug therapy</topic><topic>Urinary system involvement in other diseases. Miscellaneous</topic><topic>Urinary tract. Prostate gland</topic><topic>Urination - drug effects</topic><topic>Urination - physiology</topic><topic>Urology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Behr-Roussel, Delphine</creatorcontrib><creatorcontrib>Oger, Stéphanie</creatorcontrib><creatorcontrib>Pignol, Bernadette</creatorcontrib><creatorcontrib>Pham, Emmanuel</creatorcontrib><creatorcontrib>Le Maux, Amélie</creatorcontrib><creatorcontrib>Chabrier, Pierre-Etienne</creatorcontrib><creatorcontrib>Caisey, Stéphanie</creatorcontrib><creatorcontrib>Compagnie, Sandrine</creatorcontrib><creatorcontrib>Picaut, Philippe</creatorcontrib><creatorcontrib>Bernabé, Jacques</creatorcontrib><creatorcontrib>Alexandre, Laurent</creatorcontrib><creatorcontrib>Giuliano, François</creatorcontrib><creatorcontrib>Denys, Pierre</creatorcontrib><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>MEDLINE - Academic</collection><jtitle>European urology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Behr-Roussel, Delphine</au><au>Oger, Stéphanie</au><au>Pignol, Bernadette</au><au>Pham, Emmanuel</au><au>Le Maux, Amélie</au><au>Chabrier, Pierre-Etienne</au><au>Caisey, Stéphanie</au><au>Compagnie, Sandrine</au><au>Picaut, Philippe</au><au>Bernabé, Jacques</au><au>Alexandre, Laurent</au><au>Giuliano, François</au><au>Denys, Pierre</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Minimal Effective Dose of Dysport and Botox in a Rat Model of Neurogenic Detrusor Overactivity</atitle><jtitle>European urology</jtitle><addtitle>Eur Urol</addtitle><date>2012-05-01</date><risdate>2012</risdate><volume>61</volume><issue>5</issue><spage>1054</spage><epage>1061</epage><pages>1054-1061</pages><issn>0302-2838</issn><eissn>1873-7560</eissn><coden>EUURAV</coden><abstract><![CDATA[Abstract Background Two botulinum toxins A have been evaluated for the treatment of refractory neurogenic detrusor overactivity (NDO) in humans: Dysport (abobotulinumtoxinA) and Botox (onabotulinumtoxinA). However, these two distinct commercialized products have different potency units and are not interchangeable. Objective Assessment of the dose response and determination of minimal effective dose (MED) for Dysport and Botox in spinal cord–injured (SCI) rats with NDO. Design, setting, and participants Female, adult, Sprague-Dawley rats ( n = 98) underwent T8-T9 spinal cord transection. Nineteen days after spinal cord injury, rats received intradetrusor injections (25 μl injected, eight sites) of vehicle (V); Dysport 2, 5, 7.5, 10, and 12.5 U; and Botox 0.8, 2, 5, 7.5, and 10 U. Two days after injection, continuous cystometry was performed in conscious rats. Measurements Voiding contractions (VC) were assessed by duration of VC, intercontraction interval, voided volume, maximal pressure, pressure threshold change, and intravesical baseline pressure (BP), while nonvoiding contractions (NVC) were evaluated by amplitude, frequency, and volume threshold to elicit NVC. MEDs for Dysport and Botox were determined by analysis of variance step-down trend test. Results and limitations MEDs for Dysport and Botox were 10 U and 7.5 U, respectively. Regarding VC, only BP significantly decreased after 10 U Dysport and 7.5 U Botox compared to V (from 3.7 ± 0.6 to 1.5 ± 0.1 and 1.4 ± 0.3 mm Hg, respectively; p < 0.01 and p < 0.001, respectively). Dysport (10 U) and Botox (7.5 U) significantly inhibited NVC by decreasing their amplitude (from 7.4 ± 1.1 to 5.8 ± 0.5 and 5.4 ± 0.6 mm Hg, respectively; p < 0.05); frequency (from 2.2 ± 0.4 to 1.5 ± 0.2 and 1.3 ± 0.3 NVC per minute, respectively; p < 0.01); and increasing volume threshold to elicit NVC (from 29.8 ± 3.7 to 47.6 ± 6.9 and 47.7 ± 6.3%, respectively; p < 0.05 and p < 0.001, respectively). Conclusions This is the first preclinical dose-ranging study with Dysport and Botox under standardized conditions showing similar inhibiting effects on NDO, albeit at different MEDs. It highlights the importance of distinguishing each preparation for predicted outcomes and doses to be used. Further studies in patients with NDO are warranted to confirm these experimental results.]]></abstract><cop>Kidlington</cop><pub>Elsevier B.V</pub><pmid>22341129</pmid><doi>10.1016/j.eururo.2012.01.051</doi><tpages>8</tpages></addata></record> |
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| subjects | AbobotulinumtoxinA Animals Biological and medical sciences Botulinum Toxins, Type A - administration & dosage Cerebrospinal fluid. Meninges. Spinal cord Cystometry Disease Models, Animal Dose-Response Relationship, Drug Experimental pharmacology Female Medical sciences Nephrology. Urinary tract diseases Nervous system (semeiology, syndromes) Neurology OnabotulinumtoxinA Rats Rats, Sprague-Dawley Spinal Cord Injuries - physiopathology Spinal cord injury Treatment Outcome Urinary Bladder, Neurogenic - drug therapy Urinary Bladder, Overactive - drug therapy Urinary system involvement in other diseases. Miscellaneous Urinary tract. Prostate gland Urination - drug effects Urination - physiology Urology |
| title | Minimal Effective Dose of Dysport and Botox in a Rat Model of Neurogenic Detrusor Overactivity |
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