title: Cutaneous iontophoresis of treprostinil, a prostacyclin analog, increases microvascular blood flux in diabetic malleolus area.
abstract: Diabetic foot ulcers are one of the most common and serious complications of diabetes mellitus. Few drugs are effective in enhancing the healing of microvascular skin ulcers. The main objective of the present study was to determine whether iontophoresis of treprostinil, a prostacyclin analog, increases skin microvascular blood flux in the malleolus area of healthy subjects and diabetic patients. We recruited 12 healthy subjects and 12 type 2 diabetic patients. Cathodal iontophoresis (40mC/cm²) of treprostinil 250µM and NaCl 0.9% was performed in the malleolus area. Skin hyperemia was quantified using non-invasive laser speckle contrast imaging, and expressed as the area under the curve (AUC) of cutaneous vascular conductance (CVC). In healthy controls and diabetic patients, treprostinil 250µM induced a significant increase in CVC compared with NaCl (for diabetic patients, AUC0-6h was 19970±8697; versus 2893±5481%BL.min, respectively; P=0.002). In both groups, the peak flux was obtained between 30min and 1h after the end of treprostinil iontophoresis and flux remained higher than baseline up to 6h after ending of iontophoresis. No significant side-effect occurred. Cutaneous iontophoresis of 250µM treprostinil increases microvascular blood flux in the malleolus area in healthy volunteers and diabetic patients, without inducing systemic or local side-effects. Treprostinil cathodal iontophoresis should be further investigated as a new local therapy for diabetic ulcers.
authors.affiliation: Inserm CIC1406, Clinical Pharmacology Department, University Hospital, Grenoble, France; Noninvasive Cardiac Diagnostics Department, Medical University, Gdansk, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Hellmann
authors.affiliation: Inserm CIC1406, Clinical Pharmacology Department, University Hospital, Grenoble, France; Inserm HP2, Grenoble, France; Univ. Grenoble-Alpes, HP2, Grenoble, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Roustit
authors.affiliation: Inserm CIC1406, Clinical Pharmacology Department, University Hospital, Grenoble, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Gaillard-Bigot
authors.affiliation: Inserm CIC1406, Clinical Pharmacology Department, University Hospital, Grenoble, France; Inserm HP2, Grenoble, France; Univ. Grenoble-Alpes, HP2, Grenoble, France. Electronic address: Jean-Luc.Cracowski@ujf-grenoble.fr.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Cracowski
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D000842:Ankle / Q000098:blood supply*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D011464:Epoprostenol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D006801:Humans; D007478:Iontophoresis; D008297:Male; D008833:Microcirculation / Q000187:drug effects* / Q000502:physiology; D008875:Middle Aged; D012867:Skin / Q000098:blood supply* / Q000187:drug effects; D055815:Young Adult
chemical_list: D011464:Epoprostenol; C427248:treprostinil
keywords: Diabetic foot ulcers; Iontophoresis; Laser speckle contrast imaging; Microcirculation; Prostacyclin; Sodium chloride (PubChem CID: 5234); Treprostinil; Treprostinil (PubChem CID: 6918140)