title: Cathodal iontophoresis of treprostinil and iloprost induces a sustained increase in cutaneous flux in rats.
abstract: OBJECTIVE
  The treatment of scleroderma-related digital ulcers is still a therapeutic challenge. The most effective drugs are prostacyclin analogues. However, their usage is limited to an intravenous route of administration and by their frequent side effects. The objective of this study was to test whether treprostinil, iloprost and epoprostenol can induce sustained vasodilatation in rats when delivered locally using cutaneous iontophoresis.
  
  
  METHODS
  Treprostinil, iloprost and epoprostenol were delivered by cathodal and anodal iontophoresis onto the hindquarters of anaesthesized rats (n= 8 for each group). Skin blood flow was quantified using laser Doppler imaging and cutaneous tolerance was assessed from day 0 to day 3.
  
  
  RESULTS
  Cathodal but not anodal iontophoresis of treprostinil (6.4 mM), iloprost (0.2 mM) and epoprostenol (1.4 mM) induced a significant and sustained increase in cutaneous blood flow. The effects of treprostinil and iloprost were significantly different from those of treprostinil vehicle. Only weak effects were observed when both drugs were applied locally without current. Skin resistance was unchanged in areas treated with prostacyclin analogues. Finally, skin tolerance was good, with no evidence of epidermal damage.
  
  
  CONCLUSIONS
  Cathodal iontophoresis of treprostinil and iloprost increases cutaneous blood flow with a good local tolerance. The effects of cathodal iontophoresis of these drugs should be investigated in humans, as they could have potential as new local therapies for digital ulcers in patients with scleroderma.
authors.affiliation: Inserm ERI17, Grenoble Medical School, University Grenoble 1, Grenoble, France.
authors.forename: S
authors.initials: S
authors.lastname: Blaise
authors.forename: M
authors.initials: M
authors.lastname: Roustit
authors.forename: C
authors.initials: C
authors.lastname: Millet
authors.forename: C
authors.initials: C
authors.lastname: Ribuot
authors.forename: J
authors.initials: J
authors.lastname: Boutonnat
authors.forename: J L
authors.initials: JL
authors.lastname: Cracowski
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D004566:Electrodes; D011464:Epoprostenol / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006439:Hemodynamics; D006801:Humans; D016285:Iloprost / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D007478:Iontophoresis; D008297:Male; D009599:Nitroprusside / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000187:drug effects*
chemical_list: D000959:Antihypertensive Agents; D009599:Nitroprusside; D011464:Epoprostenol; D016285:Iloprost; C427248:treprostinil