Treprostinil Hydrogel Iontophoresis in Systemic Sclerosis-Related Digital Skin Ulcers: A Safety Study.
Administration, Cutaneous
Adult
Blood Circulation
/ drug effects
Double-Blind Method
Epoprostenol
/ administration & dosage
Female
Fingers
/ blood supply
Foot
/ blood supply
Healthy Volunteers
Humans
Hydrogels
/ adverse effects
Iontophoresis
/ adverse effects
Male
Middle Aged
Scleroderma, Systemic
/ drug therapy
Skin
/ blood supply
Skin Temperature
/ drug effects
Skin Ulcer
/ complications
Toes
/ blood supply
Young Adult
microcirculation
prostacyclin
skin
systemic sclerosis
treprostinil
Journal
Journal of clinical pharmacology
ISSN: 1552-4604
Titre abrégé: J Clin Pharmacol
Pays: England
ID NLM: 0366372
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
16
10
2019
accepted:
02
12
2019
pubmed:
23
2
2020
medline:
22
6
2021
entrez:
22
2
2020
Statut:
ppublish
Résumé
Digital skin ulcers are a severe complication of systemic sclerosis. The first-line treatment is intravenous iloprost, but it induces dose-limiting adverse effects. Local administration of treprostinil through skin iontophoresis may be a safe alternative. We conducted a 2-stage, randomized, placebo-controlled single-ascending-dose study in healthy volunteers and patients with systemic sclerosis-related 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-mg/mL hydrogel of treprostinil. We then randomly treated systemic sclerosis-related 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-point CTCAE scale. Treprostinil iontophoresis significantly increased skin blood flux on the leg (AUC
Substances chimiques
Hydrogels
0
Epoprostenol
DCR9Z582X0
treprostinil
RUM6K67ESG
Types de publication
Clinical Trial
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
758-767Informations de copyright
© 2020, The American College of Clinical Pharmacology.
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