{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:25:27Z","timestamp":1779927927788,"version":"3.53.1"},"reference-count":11,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T00:00:00Z","timestamp":1763424000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Fundamemntal Clinical Pharma"],"published-print":{"date-parts":[[2025,12]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n Diabetic foot ulcers (DFUs) represent a serious public health problem associated with significant morbidity and health costs. Despite optimal etiologic treatment and local care, amputation is frequent, stressing the need for new treatments. The benefit of systemic administration of vasodilators, such as prostacyclin analogues, has proven efficacy in other types of skin ulcers, but it is counterbalanced by potentially serious vasodilation\u2010induced, concentration\u2010dependent, adverse effects. Experimental data has shown the feasibility of local administration of treprostinil on the wound using iontophoresis.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n We aimed to assess the safety of the local iontophoretic administration of treprostinil in patients with DFU through a single ascending dose safety study.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We conducted a prospective single ascending dose phase I study. Patients received a single dose of treprostinil applied via iontophoresis at a current density of 0.2\u2009mA\/cm\n 2<\/jats:sup>\n for 30\u2009min. Local and systemic adverse effects were monitored, and plasma treprostinil concentrations were measured over an 8\u2010h follow\u2010up period.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Four patients were included, and received single doses of 0.025, 0.05, 0.1, and 0.25\u2009mg\/L at 0.2\u2009mA\/cm\n 2<\/jats:sup>\n during 30\u2009min, and were followed\u2010up for 8\u2009h. All patients did not present any significant adverse effect. Plasma concentration was below <\u20091.8\u2009ng\/mL 8\u2009h after the administration.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Our results suggest that iontophoresis of treprostinil is a safe procedure at 0.25\u2009mg\/mL, without systemic adverse effect, suggesting its potential as a targeted treatment for DFUs.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/fcp.70054","type":"journal-article","created":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T07:35:24Z","timestamp":1763537724000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Treprostinil Iontophoresis in Diabetic Foot Ulcers: A Single Ascending Dose Safety Study"],"prefix":"10.1111","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7203-8134","authenticated-orcid":false,"given":"Alicia","family":"Guigui","sequence":"first","affiliation":[{"name":"Univ. Grenoble Alpes, Inserm U1300 HP2, CHU Grenoble Alpes Grenoble France"},{"name":"Univ. Grenoble Alpes, Inserm CIC1406, CHU Grenoble Alpes Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enkeledja","family":"Hodaj","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes, Inserm CIC1406, CHU Grenoble Alpes Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Muller","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes, Department of Endocrinology CHU Grenoble Alpes Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7oise","family":"Stanke\u2010Labesque","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes, Inserm U1300 HP2, CHU Grenoble Alpes Grenoble France"},{"name":"Laboratory of Pharmacology, Pharmacogenetics and Toxicology CHU Grenoble Alpes Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Blaise","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes, Inserm U1300 HP2, CHU Grenoble Alpes Grenoble France"},{"name":"Univ. Grenoble Alpes, Department of Vascular Medicine CHU Grenoble Alpes Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0787-1469","authenticated-orcid":false,"given":"Jean\u2010Luc","family":"Cracowski","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes, Inserm U1300 HP2, CHU Grenoble Alpes Grenoble France"},{"name":"Univ. Grenoble Alpes, Pharmacovigilance Unit CHU Grenoble Alpes Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthieu","family":"Roustit","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes, Inserm U1300 HP2, CHU Grenoble Alpes Grenoble France"},{"name":"Univ. Grenoble Alpes, Inserm CIC1406, CHU Grenoble Alpes Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,18]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.10578"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-89869-8_10"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2010.01045.x"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2013.255"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1574"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2015.03.066"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04925"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcibr066496"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc14-S081"},{"issue":"8","key":"e_1_2_11_11_1","first-page":"60","article-title":"The University of Texas Diabetic Foot Classification System","volume":"42","author":"Armstrong D. G.","year":"1996","journal-title":"Ostomy\/Wound Management"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12128"}],"container-title":["Fundamental & Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/fcp.70054","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T08:15:17Z","timestamp":1764404117000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/fcp.70054"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,18]]},"references-count":11,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1111\/fcp.70054"],"URL":"https:\/\/doi.org\/10.1111\/fcp.70054","archive":["Portico"],"relation":{},"ISSN":["0767-3981","1472-8206"],"issn-type":[{"value":"0767-3981","type":"print"},{"value":"1472-8206","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,18]]},"assertion":[{"value":"2024-10-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70054"}}