Cutaneous iontophoresis of treprostinil in systemic sclerosis: a proof-of-concept study.
Ischemic digital ulcer (DU) is a serious complication of systemic sclerosis (SSc). Intravenous prostanoids are the only approved treatment for active DUs, but they induce dose-limiting side effects and require hospitalization. Our objective was to evaluate the effect of iontophoresis (a noninvasive drug delivery method) of treprostinil in SSc patients. Three studies were conducted: a pharmacokinetic study in 12 healthy volunteers showed that peak dermal concentration was reached at 2 hours, whereas plasma treprostinil was undetected. Then, a placebo-controlled, double-blind incremental dose study assessed the effect of treprostinil on digital skin blood flow in 22 healthy subjects. The effect of the highest dose was then compared with that of placebo in 12 SSc patients. Treprostinil significantly increased skin blood flow in healthy subjects (P = 0.006) and in SSc patients (P = 0.023). In conclusion, digital iontophoresis of treprostinil is feasible, is well tolerated, and increases digital skin perfusion. It could be tested as a treatment for SSc-related DUs.
1] UMR 1042-HP2, INSERM and University Grenoble-Alpes, Grenoble, France [2] Clinical Pharmacology Unit, INSERM CIC1406, Grenoble University Hospital, Grenoble, France.
M
M
Roustit
UMR 1042-HP2, INSERM and University Grenoble-Alpes, Grenoble, France.
F
F
Gaillard-Bigot
1] UMR 1042-HP2, INSERM and University Grenoble-Alpes, Grenoble, France [2] Vascular Medicine Department, Grenoble University Hospital, Grenoble, France.
S
S
Blaise
1] UMR 1042-HP2, INSERM and University Grenoble-Alpes, Grenoble, France [2] Laboratory of Pharmacology, Grenoble University Hospital, Grenoble, France.
F
F
Stanke-Labesque
Clinical Pharmacology Unit, INSERM CIC1406, Grenoble University Hospital, Grenoble, France.
C
C
Cracowski
Vascular Medicine Department, Grenoble University Hospital, Grenoble, France.
C
C
Seinturier
Laboratory of Pharmacology, Grenoble University Hospital, Grenoble, France.
J-F
JF
Jourdil
Vascular Medicine Department, Grenoble University Hospital, Grenoble, France.
B
B
Imbert
Vascular Medicine Department, Grenoble University Hospital, Grenoble, France.
P H
PH
Carpentier
1] UMR 1042-HP2, INSERM and University Grenoble-Alpes, Grenoble, France [2] Clinical Pharmacology Unit, INSERM CIC1406, Grenoble University Hospital, Grenoble, France.
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JL
Cracowski
D000279:Administration, Cutaneous; D000293:Adolescent; D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D011464:Epoprostenol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D005240:Feasibility Studies; D005260:Female; D005385:Fingers / Q000098:blood supply; D006801:Humans; D007478:Iontophoresis; D008297:Male; D008875:Middle Aged; D012039:Regional Blood Flow / Q000187:drug effects; D012595:Scleroderma, Systemic / Q000150:complications / Q000188:drug therapy*; D012867:Skin / Q000098:blood supply; D012883:Skin Ulcer / Q000209:etiology / Q000517:prevention & control*; D014018:Tissue Distribution; D055815:Young Adult
D000959:Antihypertensive Agents; D011464:Epoprostenol; C427248:treprostinil