{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:39:22Z","timestamp":1791920362309,"version":"4.3.4"},"reference-count":13,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2017,9,6]],"date-time":"2017-09-06T00:00:00Z","timestamp":1504656000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Cutanea Life Science, Wayne, Pennsylvania, USA"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Acad Dermatol Venereol"],"published-print":{"date-parts":[[2017,12]]},"abstract":"Abstract<\/jats:title>Background<\/jats:title>DNA<\/jats:styled-content> viruses such as HPV<\/jats:styled-content> rely on K+<\/jats:sup> influx for replication. Both digoxin and furosemide inhibit the K+<\/jats:sup> influx by interacting with cell membrane ion co\u2010transporters (Na+<\/jats:sup>\/K+<\/jats:sup>\u2010ATP<\/jats:styled-content>ase and Na+<\/jats:sup>\u2010K+<\/jats:sup>\u20102Cl\u2212<\/jats:sup> co\u2010transporter\u20101, respectively). We therefore hypothesized that these two compounds in a topical formulation may be valuable in the treatment of HPV<\/jats:styled-content>\u2010induced warts. This new approach is called Ionic Contra\u2010Viral Therapy (ICVT<\/jats:styled-content>).<\/jats:p><\/jats:sec>Objective<\/jats:title>To evaluate systemic exposure, safety and tolerability of ICVT<\/jats:styled-content> with a combination of furosemide and digoxin after repeated topical application in subjects with common warts. Furthermore, we aimed to evaluate pharmacodynamics effects of ICVT<\/jats:styled-content>.<\/jats:p><\/jats:sec>Methods<\/jats:title>Twelve healthy subjects with at least four common warts on their hands were included in the study and treated with a fixed dose of 980\u00a0mg topical gel containing 0.125% (w\/w) digoxin and 0.125% (w\/w) furosemide for 7 consecutive days on their lower back to assess safety and systemic exposure. Two warts were treated with 10\u00a0mg each and two served as negative controls to obtain preliminary evidence of treatment effect.<\/jats:p><\/jats:sec>Results<\/jats:title>ICVT<\/jats:styled-content> was well tolerated topically, and there was no evidence of systemic exposure of digoxin or furosemide. There were no clinical relevant safety findings and no serious adverse events (SAE<\/jats:styled-content>s). A rapid and statistically significant reduction in diameter, height and volume of the warts was already observed at day 14.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>ICVT<\/jats:styled-content> was found to be safe for administration to humans and 7\u00a0days of active treatment showed a statistical significant wart reduction compared to untreated control lesions, clearly indicating pharmacological activity.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdv.14527","type":"journal-article","created":{"date-parts":[[2017,8,17]],"date-time":"2017-08-17T16:32:39Z","timestamp":1502987559000},"page":"2088-2090","source":"Crossref","is-referenced-by-count":20,"title":["Topical ionic contra\u2010viral therapy comprised of digoxin and furosemide as a potential novel treatment approach for common warts"],"prefix":"10.1111","volume":"31","author":[{"given":"T.","family":"van der Kolk","sequence":"first","affiliation":[{"name":"Centre for Human Drug Research Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.R.","family":"Dillingh","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Rijneveld","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.S.","family":"Klaassen","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.N.C.","family":"de Koning","sequence":"additional","affiliation":[{"name":"DDL Diagnostic Laboratory Rijswijk The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.T.P.","family":"Kouwenhoven","sequence":"additional","affiliation":[{"name":"Department of Dermatology Leiden University Medical Centre Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.E.","family":"Genders","sequence":"additional","affiliation":[{"name":"Department of Dermatology Leiden University Medical Centre Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. N.","family":"Bouwes Bavinck","sequence":"additional","affiliation":[{"name":"Department of Dermatology Leiden University Medical Centre Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Feiss","sequence":"additional","affiliation":[{"name":"Cutanea Life Science Wayne PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Rissmann","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Burggraaf","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,9,6]]},"reference":[{"key":"e_1_2_3_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-0960.1996.tb01010.x"},{"issue":"2","key":"e_1_2_3_3_1","first-page":"55","article-title":"The population incidence of warts","author":"Beliaeva TL","year":"1990","journal-title":"Vestn Dermatol Venerol"},{"key":"e_1_2_3_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-3083.2006.01833.x"},{"key":"e_1_2_3_5_1","doi-asserted-by":"publisher","DOI":"10.1370\/afm.1508"},{"key":"e_1_2_3_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2009.09160.x"},{"key":"e_1_2_3_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2012.07.014"},{"key":"e_1_2_3_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2011.06.016"},{"key":"e_1_2_3_9_1","doi-asserted-by":"publisher","DOI":"10.1503\/cmaj.092194"},{"key":"e_1_2_3_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2015.1"},{"key":"e_1_2_3_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2011.10218.x"},{"issue":"9","key":"e_1_2_3_12_1","first-page":"CD001781","article-title":"Topical treatments for cutaneous warts","author":"Kwok CS","year":"2012","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_3_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00705-006-0824-x"},{"key":"e_1_2_3_14_1","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.02122-09"}],"container-title":["Journal of the European Academy of Dermatology and Venereology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjdv.14527","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jdv.14527","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T13:16:56Z","timestamp":1695561416000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jdv.14527"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,9,6]]},"references-count":13,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2017,12]]}},"alternative-id":["10.1111\/jdv.14527"],"URL":"https:\/\/doi.org\/10.1111\/jdv.14527","archive":["Portico"],"relation":{},"ISSN":["0926-9959","1468-3083"],"issn-type":[{"value":"0926-9959","type":"print"},{"value":"1468-3083","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,9,6]]}}}