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Effects of Injectable HPβCD-Diclofenac on the Human Delayed Rectifier Potassium Channel Current In Vitro and on Proarrhythmic QTc In Vivo
Abstract Background Novel formulations and administration routes of established drugs may result in higher maximum concentrations or total exposures and potentially cause previously unrecognized adverse events. Objective This study evaluated the proarrhythmic potential of hydroxypropyl-β-cyclodextri...
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| Published in: | Clinical therapeutics 2013-05, Vol.35 (5), p.646-658 |
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| creator | Carr, Daniel B., MD McDonnell Moorehead, Tara, BA Bouchard, Annie, MSc Sprenger, Craig R., MD Hamilton, Douglas A., MBA Lang, Eric, MD Madden, Donna, MS Lacouture, Peter G., PhD Wright, Curtis, MD, MPH |
| description | Abstract Background Novel formulations and administration routes of established drugs may result in higher maximum concentrations or total exposures and potentially cause previously unrecognized adverse events. Objective This study evaluated the proarrhythmic potential of hydroxypropyl-β-cyclodextrin (HPβCD)-diclofenac, a novel injectable diclofenac formulation solubilized with hydroxypropyl-β-cyclodextrin (HPβCD), on ventricular electrical conduction in preclinical and clinical models. Methods We assessed the effects of diclofenac, HPβCD, and HPβCD-diclofenac on the human delayed rectifier potassium channel (IKr ) using human embryonic kidney (HEK) 293 cells transfected with a human ether-à-go-go–related gene (hERG) using whole-cell patch-clamp. In a single-dose, active- and placebo-controlled, 4-period crossover, thorough QT in vivo study, 70 healthy volunteers (mean age, 23.3 years; range, 18–49 years; 55.75% male) received HPβCD-diclofenac at 37.5- and 75-mg doses, inactive vehicle (placebo), and an active control (moxifloxacin). Results In vitro, diclofenac produced no statistically significant effect on IKr . Significant, non–dose-dependent effects were observed in the presence of HPβCD or HPβCD-diclofenac of similar magnitude across the 300-fold dose range of concentrations tested, suggesting an artifact due to the detergent effect of HPβCD in this in vitro model. In vivo, neither HPβCD-diclofenac dose resulted in QTc prolongation ≥2 ms (≥5 ms is the threshold of clinical concern). No correlation was evident between changes in QTc and plasma concentrations of diclofenac or HPβCD. Confirming study sensitivity, moxifloxacin produced a mean QTc prolongation >10 ms. Conclusions The findings from the present study suggest that HPβCD-diclofenac does not have a dose-dependent effect in the in vitro hERG assay system and does not produce proarrhythmic QTc prolongation in vivo. ClinicalTrials.gov identifier: NCT01812538. |
| doi_str_mv | 10.1016/j.clinthera.2013.03.014 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1353984605</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>1_s2_0_S0149291813001276</els_id><sourcerecordid>1353984605</sourcerecordid><originalsourceid>FETCH-LOGICAL-c505t-ea3067e3be79948a6346d879abe59109e8e9793504c6a8c84ff5915f0bcfb5543</originalsourceid><addsrcrecordid>eNqNktGK1DAUhoso7rj6CpobwZuOSdOkzY2wdFZnYcFRV_EupOkJk9oma9IuzCv4OD6Iz2TKjCt4JRxIOHz5_-Q_ybIXBK8JJvx1v9aDddMegloXmNA1TkXKB9mK1JXICSm_PsxWqSPyQpD6LHsSY48xpoIVj7OzgrKq5pivsh-XxoCeIvIGXbk-bVU7ANrufv1sNvnG6sEbcEoj71CyQ9t5VA5tYFAH6NDHxFtjIaCdn1SMdh5Rs1fOwYCaOQRwU1JFX-wUPFKuW1R2wasQ9odpP1qNPtzoI3Hnn2aPjBoiPDut59nnt5c3zTa_fv_uqrm4zjXDbMpBUcwroC1UQpS14rTkXXq0aoEJggXUICpBGS41V7WuS2NSnxncatMyVtLz7NVR9zb47zPESY42ahgG5cDPURLKqKhLjllCqyOqg48xgJG3wY4qHCTBchmE7OX9IOQyCIlTkcXk-clkbkfo7s_9ST4BL0-AiloNJiinbfzLVSXmJV-4iyMHKZK7FLWM2oLT0NmQ0pedt_9xmTf_aCycTbbf4ACx93NwKXFJZCwklp-Wf7N8G0IxJkXF6W9TSMCO</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1353984605</pqid></control><display><type>article</type><title>Effects of Injectable HPβCD-Diclofenac on the Human Delayed Rectifier Potassium Channel Current In Vitro and on Proarrhythmic QTc In Vivo</title><source>ScienceDirect Freedom Collection 2022-2024</source><creator>Carr, Daniel B., MD ; McDonnell Moorehead, Tara, BA ; Bouchard, Annie, MSc ; Sprenger, Craig R., MD ; Hamilton, Douglas A., MBA ; Lang, Eric, MD ; Madden, Donna, MS ; Lacouture, Peter G., PhD ; Wright, Curtis, MD, MPH</creator><creatorcontrib>Carr, Daniel B., MD ; McDonnell Moorehead, Tara, BA ; Bouchard, Annie, MSc ; Sprenger, Craig R., MD ; Hamilton, Douglas A., MBA ; Lang, Eric, MD ; Madden, Donna, MS ; Lacouture, Peter G., PhD ; Wright, Curtis, MD, MPH</creatorcontrib><description>Abstract Background Novel formulations and administration routes of established drugs may result in higher maximum concentrations or total exposures and potentially cause previously unrecognized adverse events. Objective This study evaluated the proarrhythmic potential of hydroxypropyl-β-cyclodextrin (HPβCD)-diclofenac, a novel injectable diclofenac formulation solubilized with hydroxypropyl-β-cyclodextrin (HPβCD), on ventricular electrical conduction in preclinical and clinical models. Methods We assessed the effects of diclofenac, HPβCD, and HPβCD-diclofenac on the human delayed rectifier potassium channel (IKr ) using human embryonic kidney (HEK) 293 cells transfected with a human ether-à-go-go–related gene (hERG) using whole-cell patch-clamp. In a single-dose, active- and placebo-controlled, 4-period crossover, thorough QT in vivo study, 70 healthy volunteers (mean age, 23.3 years; range, 18–49 years; 55.75% male) received HPβCD-diclofenac at 37.5- and 75-mg doses, inactive vehicle (placebo), and an active control (moxifloxacin). Results In vitro, diclofenac produced no statistically significant effect on IKr . Significant, non–dose-dependent effects were observed in the presence of HPβCD or HPβCD-diclofenac of similar magnitude across the 300-fold dose range of concentrations tested, suggesting an artifact due to the detergent effect of HPβCD in this in vitro model. In vivo, neither HPβCD-diclofenac dose resulted in QTc prolongation ≥2 ms (≥5 ms is the threshold of clinical concern). No correlation was evident between changes in QTc and plasma concentrations of diclofenac or HPβCD. Confirming study sensitivity, moxifloxacin produced a mean QTc prolongation >10 ms. Conclusions The findings from the present study suggest that HPβCD-diclofenac does not have a dose-dependent effect in the in vitro hERG assay system and does not produce proarrhythmic QTc prolongation in vivo. ClinicalTrials.gov identifier: NCT01812538.</description><identifier>ISSN: 0149-2918</identifier><identifier>EISSN: 1879-114X</identifier><identifier>DOI: 10.1016/j.clinthera.2013.03.014</identifier><identifier>PMID: 23578606</identifier><language>eng</language><publisher>Bridgewater, NJ: Elsevier Inc</publisher><subject>2-Hydroxypropyl-beta-cyclodextrin ; Adolescent ; Adult ; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage ; Anti-Inflammatory Agents, Non-Steroidal - adverse effects ; Anti-Inflammatory Agents, Non-Steroidal - chemistry ; Arrhythmias, Cardiac - chemically induced ; Aza Compounds - adverse effects ; beta-Cyclodextrins - chemistry ; Biological and medical sciences ; Cross-Over Studies ; cyclodextrin ; diclofenac ; Diclofenac - administration & dosage ; Diclofenac - adverse effects ; Diclofenac - chemistry ; Dose-Response Relationship, Drug ; ERG1 Potassium Channel ; Ether-A-Go-Go Potassium Channels - metabolism ; Female ; Fluoroquinolones ; HEK293 Cells ; Humans ; Internal Medicine ; Long QT Syndrome - chemically induced ; Male ; Medical Education ; Medical sciences ; Middle Aged ; pain ; Patch-Clamp Techniques ; Pharmacology. Drug treatments ; Potassium Channels, Inwardly Rectifying - drug effects ; QT interval ; Quinolines - adverse effects ; Young Adult</subject><ispartof>Clinical therapeutics, 2013-05, Vol.35 (5), p.646-658</ispartof><rights>Elsevier HS Journals, Inc.</rights><rights>2013 Elsevier HS Journals, Inc.</rights><rights>2014 INIST-CNRS</rights><rights>Copyright © 2013 Elsevier HS Journals, Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c505t-ea3067e3be79948a6346d879abe59109e8e9793504c6a8c84ff5915f0bcfb5543</citedby><cites>FETCH-LOGICAL-c505t-ea3067e3be79948a6346d879abe59109e8e9793504c6a8c84ff5915f0bcfb5543</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=27406466$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23578606$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Carr, Daniel B., MD</creatorcontrib><creatorcontrib>McDonnell Moorehead, Tara, BA</creatorcontrib><creatorcontrib>Bouchard, Annie, MSc</creatorcontrib><creatorcontrib>Sprenger, Craig R., MD</creatorcontrib><creatorcontrib>Hamilton, Douglas A., MBA</creatorcontrib><creatorcontrib>Lang, Eric, MD</creatorcontrib><creatorcontrib>Madden, Donna, MS</creatorcontrib><creatorcontrib>Lacouture, Peter G., PhD</creatorcontrib><creatorcontrib>Wright, Curtis, MD, MPH</creatorcontrib><title>Effects of Injectable HPβCD-Diclofenac on the Human Delayed Rectifier Potassium Channel Current In Vitro and on Proarrhythmic QTc In Vivo</title><title>Clinical therapeutics</title><addtitle>Clin Ther</addtitle><description>Abstract Background Novel formulations and administration routes of established drugs may result in higher maximum concentrations or total exposures and potentially cause previously unrecognized adverse events. Objective This study evaluated the proarrhythmic potential of hydroxypropyl-β-cyclodextrin (HPβCD)-diclofenac, a novel injectable diclofenac formulation solubilized with hydroxypropyl-β-cyclodextrin (HPβCD), on ventricular electrical conduction in preclinical and clinical models. Methods We assessed the effects of diclofenac, HPβCD, and HPβCD-diclofenac on the human delayed rectifier potassium channel (IKr ) using human embryonic kidney (HEK) 293 cells transfected with a human ether-à-go-go–related gene (hERG) using whole-cell patch-clamp. In a single-dose, active- and placebo-controlled, 4-period crossover, thorough QT in vivo study, 70 healthy volunteers (mean age, 23.3 years; range, 18–49 years; 55.75% male) received HPβCD-diclofenac at 37.5- and 75-mg doses, inactive vehicle (placebo), and an active control (moxifloxacin). Results In vitro, diclofenac produced no statistically significant effect on IKr . Significant, non–dose-dependent effects were observed in the presence of HPβCD or HPβCD-diclofenac of similar magnitude across the 300-fold dose range of concentrations tested, suggesting an artifact due to the detergent effect of HPβCD in this in vitro model. In vivo, neither HPβCD-diclofenac dose resulted in QTc prolongation ≥2 ms (≥5 ms is the threshold of clinical concern). No correlation was evident between changes in QTc and plasma concentrations of diclofenac or HPβCD. Confirming study sensitivity, moxifloxacin produced a mean QTc prolongation >10 ms. Conclusions The findings from the present study suggest that HPβCD-diclofenac does not have a dose-dependent effect in the in vitro hERG assay system and does not produce proarrhythmic QTc prolongation in vivo. ClinicalTrials.gov identifier: NCT01812538.</description><subject>2-Hydroxypropyl-beta-cyclodextrin</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - administration & dosage</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - adverse effects</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - chemistry</subject><subject>Arrhythmias, Cardiac - chemically induced</subject><subject>Aza Compounds - adverse effects</subject><subject>beta-Cyclodextrins - chemistry</subject><subject>Biological and medical sciences</subject><subject>Cross-Over Studies</subject><subject>cyclodextrin</subject><subject>diclofenac</subject><subject>Diclofenac - administration & dosage</subject><subject>Diclofenac - adverse effects</subject><subject>Diclofenac - chemistry</subject><subject>Dose-Response Relationship, Drug</subject><subject>ERG1 Potassium Channel</subject><subject>Ether-A-Go-Go Potassium Channels - metabolism</subject><subject>Female</subject><subject>Fluoroquinolones</subject><subject>HEK293 Cells</subject><subject>Humans</subject><subject>Internal Medicine</subject><subject>Long QT Syndrome - chemically induced</subject><subject>Male</subject><subject>Medical Education</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>pain</subject><subject>Patch-Clamp Techniques</subject><subject>Pharmacology. Drug treatments</subject><subject>Potassium Channels, Inwardly Rectifying - drug effects</subject><subject>QT interval</subject><subject>Quinolines - adverse effects</subject><subject>Young Adult</subject><issn>0149-2918</issn><issn>1879-114X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><recordid>eNqNktGK1DAUhoso7rj6CpobwZuOSdOkzY2wdFZnYcFRV_EupOkJk9oma9IuzCv4OD6Iz2TKjCt4JRxIOHz5_-Q_ybIXBK8JJvx1v9aDddMegloXmNA1TkXKB9mK1JXICSm_PsxWqSPyQpD6LHsSY48xpoIVj7OzgrKq5pivsh-XxoCeIvIGXbk-bVU7ANrufv1sNvnG6sEbcEoj71CyQ9t5VA5tYFAH6NDHxFtjIaCdn1SMdh5Rs1fOwYCaOQRwU1JFX-wUPFKuW1R2wasQ9odpP1qNPtzoI3Hnn2aPjBoiPDut59nnt5c3zTa_fv_uqrm4zjXDbMpBUcwroC1UQpS14rTkXXq0aoEJggXUICpBGS41V7WuS2NSnxncatMyVtLz7NVR9zb47zPESY42ahgG5cDPURLKqKhLjllCqyOqg48xgJG3wY4qHCTBchmE7OX9IOQyCIlTkcXk-clkbkfo7s_9ST4BL0-AiloNJiinbfzLVSXmJV-4iyMHKZK7FLWM2oLT0NmQ0pedt_9xmTf_aCycTbbf4ACx93NwKXFJZCwklp-Wf7N8G0IxJkXF6W9TSMCO</recordid><startdate>20130501</startdate><enddate>20130501</enddate><creator>Carr, Daniel B., MD</creator><creator>McDonnell Moorehead, Tara, BA</creator><creator>Bouchard, Annie, MSc</creator><creator>Sprenger, Craig R., MD</creator><creator>Hamilton, Douglas A., MBA</creator><creator>Lang, Eric, MD</creator><creator>Madden, Donna, MS</creator><creator>Lacouture, Peter G., PhD</creator><creator>Wright, Curtis, MD, MPH</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>6I.</scope><scope>AAFTH</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>7X8</scope></search><sort><creationdate>20130501</creationdate><title>Effects of Injectable HPβCD-Diclofenac on the Human Delayed Rectifier Potassium Channel Current In Vitro and on Proarrhythmic QTc In Vivo</title><author>Carr, Daniel B., MD ; McDonnell Moorehead, Tara, BA ; Bouchard, Annie, MSc ; Sprenger, Craig R., MD ; Hamilton, Douglas A., MBA ; Lang, Eric, MD ; Madden, Donna, MS ; Lacouture, Peter G., PhD ; Wright, Curtis, MD, MPH</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c505t-ea3067e3be79948a6346d879abe59109e8e9793504c6a8c84ff5915f0bcfb5543</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>2-Hydroxypropyl-beta-cyclodextrin</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - administration & dosage</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - adverse effects</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - chemistry</topic><topic>Arrhythmias, Cardiac - chemically induced</topic><topic>Aza Compounds - adverse effects</topic><topic>beta-Cyclodextrins - chemistry</topic><topic>Biological and medical sciences</topic><topic>Cross-Over Studies</topic><topic>cyclodextrin</topic><topic>diclofenac</topic><topic>Diclofenac - administration & dosage</topic><topic>Diclofenac - adverse effects</topic><topic>Diclofenac - chemistry</topic><topic>Dose-Response Relationship, Drug</topic><topic>ERG1 Potassium Channel</topic><topic>Ether-A-Go-Go Potassium Channels - metabolism</topic><topic>Female</topic><topic>Fluoroquinolones</topic><topic>HEK293 Cells</topic><topic>Humans</topic><topic>Internal Medicine</topic><topic>Long QT Syndrome - chemically induced</topic><topic>Male</topic><topic>Medical Education</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>pain</topic><topic>Patch-Clamp Techniques</topic><topic>Pharmacology. Drug treatments</topic><topic>Potassium Channels, Inwardly Rectifying - drug effects</topic><topic>QT interval</topic><topic>Quinolines - adverse effects</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Carr, Daniel B., MD</creatorcontrib><creatorcontrib>McDonnell Moorehead, Tara, BA</creatorcontrib><creatorcontrib>Bouchard, Annie, MSc</creatorcontrib><creatorcontrib>Sprenger, Craig R., MD</creatorcontrib><creatorcontrib>Hamilton, Douglas A., MBA</creatorcontrib><creatorcontrib>Lang, Eric, MD</creatorcontrib><creatorcontrib>Madden, Donna, MS</creatorcontrib><creatorcontrib>Lacouture, Peter G., PhD</creatorcontrib><creatorcontrib>Wright, Curtis, MD, MPH</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</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>MEDLINE - Academic</collection><jtitle>Clinical therapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Carr, Daniel B., MD</au><au>McDonnell Moorehead, Tara, BA</au><au>Bouchard, Annie, MSc</au><au>Sprenger, Craig R., MD</au><au>Hamilton, Douglas A., MBA</au><au>Lang, Eric, MD</au><au>Madden, Donna, MS</au><au>Lacouture, Peter G., PhD</au><au>Wright, Curtis, MD, MPH</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of Injectable HPβCD-Diclofenac on the Human Delayed Rectifier Potassium Channel Current In Vitro and on Proarrhythmic QTc In Vivo</atitle><jtitle>Clinical therapeutics</jtitle><addtitle>Clin Ther</addtitle><date>2013-05-01</date><risdate>2013</risdate><volume>35</volume><issue>5</issue><spage>646</spage><epage>658</epage><pages>646-658</pages><issn>0149-2918</issn><eissn>1879-114X</eissn><notes>ObjectType-Article-2</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-News-1</notes><notes>ObjectType-Feature-3</notes><notes>content type line 23</notes><abstract>Abstract Background Novel formulations and administration routes of established drugs may result in higher maximum concentrations or total exposures and potentially cause previously unrecognized adverse events. Objective This study evaluated the proarrhythmic potential of hydroxypropyl-β-cyclodextrin (HPβCD)-diclofenac, a novel injectable diclofenac formulation solubilized with hydroxypropyl-β-cyclodextrin (HPβCD), on ventricular electrical conduction in preclinical and clinical models. Methods We assessed the effects of diclofenac, HPβCD, and HPβCD-diclofenac on the human delayed rectifier potassium channel (IKr ) using human embryonic kidney (HEK) 293 cells transfected with a human ether-à-go-go–related gene (hERG) using whole-cell patch-clamp. In a single-dose, active- and placebo-controlled, 4-period crossover, thorough QT in vivo study, 70 healthy volunteers (mean age, 23.3 years; range, 18–49 years; 55.75% male) received HPβCD-diclofenac at 37.5- and 75-mg doses, inactive vehicle (placebo), and an active control (moxifloxacin). Results In vitro, diclofenac produced no statistically significant effect on IKr . Significant, non–dose-dependent effects were observed in the presence of HPβCD or HPβCD-diclofenac of similar magnitude across the 300-fold dose range of concentrations tested, suggesting an artifact due to the detergent effect of HPβCD in this in vitro model. In vivo, neither HPβCD-diclofenac dose resulted in QTc prolongation ≥2 ms (≥5 ms is the threshold of clinical concern). No correlation was evident between changes in QTc and plasma concentrations of diclofenac or HPβCD. Confirming study sensitivity, moxifloxacin produced a mean QTc prolongation >10 ms. Conclusions The findings from the present study suggest that HPβCD-diclofenac does not have a dose-dependent effect in the in vitro hERG assay system and does not produce proarrhythmic QTc prolongation in vivo. ClinicalTrials.gov identifier: NCT01812538.</abstract><cop>Bridgewater, NJ</cop><pub>Elsevier Inc</pub><pmid>23578606</pmid><doi>10.1016/j.clinthera.2013.03.014</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0149-2918 |
| ispartof | Clinical therapeutics, 2013-05, Vol.35 (5), p.646-658 |
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| source | ScienceDirect Freedom Collection 2022-2024 |
| subjects | 2-Hydroxypropyl-beta-cyclodextrin Adolescent Adult Anti-Inflammatory Agents, Non-Steroidal - administration & dosage Anti-Inflammatory Agents, Non-Steroidal - adverse effects Anti-Inflammatory Agents, Non-Steroidal - chemistry Arrhythmias, Cardiac - chemically induced Aza Compounds - adverse effects beta-Cyclodextrins - chemistry Biological and medical sciences Cross-Over Studies cyclodextrin diclofenac Diclofenac - administration & dosage Diclofenac - adverse effects Diclofenac - chemistry Dose-Response Relationship, Drug ERG1 Potassium Channel Ether-A-Go-Go Potassium Channels - metabolism Female Fluoroquinolones HEK293 Cells Humans Internal Medicine Long QT Syndrome - chemically induced Male Medical Education Medical sciences Middle Aged pain Patch-Clamp Techniques Pharmacology. Drug treatments Potassium Channels, Inwardly Rectifying - drug effects QT interval Quinolines - adverse effects Young Adult |
| title | Effects of Injectable HPβCD-Diclofenac on the Human Delayed Rectifier Potassium Channel Current In Vitro and on Proarrhythmic QTc In Vivo |
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