{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:22:16Z","timestamp":1779927736951,"version":"3.53.1"},"reference-count":25,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,2,20]],"date-time":"2020-02-20T00:00:00Z","timestamp":1582156800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Digital skin ulcers are a severe complication of systemic sclerosis. The first\u2010line treatment is intravenous iloprost, but it induces dose\u2010limiting adverse effects. Local administration of treprostinil through skin iontophoresis may be a safe alternative. We conducted a 2\u2010stage, randomized, placebo\u2010controlled single\u2010ascending\u2010dose study in healthy volunteers and patients with systemic sclerosis\u2010related digital ulcer. We further explored the effect of the procedure on skin blood flux. In a first group of healthy subjects, treprostinil and placebo iontophoresis were performed at 3 locations (ie, 6 skin sites): the sole of the foot, the leg, and the fingers. We used a 1\u2010mg\/mL hydrogel of treprostinil. We then randomly treated systemic sclerosis\u2010related digital ulcers in a 3:1 ratio of treprostinil or placebo. We used concentrations from 0.1 to 1 mg\/mL. All adverse events were recorded and rated according to the Common Terminology Criteria for Adverse Events (CTCAE), whereas skin microvascular blood flux was recorded with laser speckle contrast imaging. Among the 12 healthy volunteers, we observed 60 local adverse effects: burns, skin pain, erythema, and pruritus, graded 1 or 2 on the 5\u2010point CTCAE scale. Treprostinil iontophoresis significantly increased skin blood flux on the leg (AUC<jats:sub>0\u20104\u00a0h<\/jats:sub> at 88\u00a0460% \u00b1 6436% versus 12\u00a0730% \u00b1 3397% baseline flux.min respectively; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.001) and on the sole of the foot (AUC<jats:sub>0\u20103 h<\/jats:sub> at 20\u00a0124% \u00b1 6119% versus 3142% \u00b1 3036% baseline flux.min, respectively; <jats:italic>P<\/jats:italic>\u00a0=\u00a0.018) with a trend on the finger. Among 5 patients with systemic sclerosis\u2010related digital ulcer, 2 resolutive local adverse effects were reported. Iontophoresis of treprostinil hydrogel was safe in systemic sclerosis patients with digital ulcer.<\/jats:p>","DOI":"10.1002\/jcph.1574","type":"journal-article","created":{"date-parts":[[2020,2,21]],"date-time":"2020-02-21T06:00:49Z","timestamp":1582264849000},"page":"758-767","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Treprostinil Hydrogel Iontophoresis in Systemic Sclerosis\u2010Related Digital Skin Ulcers: A Safety Study"],"prefix":"10.1002","volume":"60","author":[{"given":"Alicia","family":"Guigui","sequence":"first","affiliation":[{"name":"Grenoble Alpes University Hospital Clinical Pharmacology  Grenoble France"},{"name":"Univ. Grenoble Alpes  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roseline","family":"Mazet","sequence":"additional","affiliation":[{"name":"Grenoble Alpes University Hospital, Pharmacy  Grenoble France"},{"name":"Univ. Grenoble Alpes, DPM, UMR CNRS 5063, ICMG FR 2607  Saint Martin d'H\u00e8res France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Blaise","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes  Grenoble France"},{"name":"Grenoble Alpes University Hospital Department of Vascular Medicine  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Cracowski","sequence":"additional","affiliation":[{"name":"Grenoble Alpes University Hospital Clinical Pharmacology  Grenoble France"},{"name":"Univ. Grenoble Alpes  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myrtille","family":"Beau\u2010Guillaumot","sequence":"additional","affiliation":[{"name":"Grenoble Alpes University Hospital Clinical Pharmacology  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvain","family":"Kotzki","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthieu","family":"Roustit","sequence":"additional","affiliation":[{"name":"Grenoble Alpes University Hospital Clinical Pharmacology  Grenoble France"},{"name":"Univ. Grenoble Alpes  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Luc","family":"Cracowski","sequence":"additional","affiliation":[{"name":"Grenoble Alpes University Hospital Clinical Pharmacology  Grenoble France"},{"name":"Univ. 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