Vascular Effects of Treprostinil Cutaneous Iontophoresis on the Leg, Finger, and Foot

Gaillard-Bigot, Florence; Roustit, Matthieu; Jourdil, Jean-François; Stanke‐Labesque, Françoise; Cracowski, Jean‐Luc

doi:10.1002/jcph.898

Cited by 2 publications

(3 citation statements)

References 37 publications

(53 reference statements)

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“…Localized erythema was far more frequent with treprostinil, and although we reported this as an adverse effect, it was an expected pharmacodynamic effect related to its potent vasodilator properties. Indeed, increased skin blood flux was observed in the leg and foot of healthy volunteers, as seen in our previous studies with the liquid formulation of treprostinil . In the fingers only a trend was observed, probably related to the small size of the study with only 10 volunteers.…”

Section: Discussionsupporting

confidence: 72%

“…Our choice of treprostinil concentrations and vehicle was based on a previous study in healthy volunteers in which we had shown a concentration‐dependent effect up to treprostinil concentrations of 1 mg/mL on the forearm, without any safety issues related to treprostinil skin permeation . In addition, the liquid formulation of 1 mg/mL treprostinil was safe in healthy volunteers and systemic sclerosis patients without ulcerations . Therefore, as no systemic adverse effect related to treprostinil was expected, we ran the treprostinil hydrogel iontophoresis on the leg, finger, and foot in a single day for each healthy volunteer.…”

Section: Discussionmentioning

confidence: 99%

“…We previously showed that cathodal iontophoresis allows local delivery of a liquid solution of a prostacyclin analogue, treprostinil, into the dermis, with limited systemic diffusion . When performed on intact human skin, the procedure induces a sustained increase in cutaneous perfusion at the forearm, fingers, and feet and is well tolerated …”

mentioning

confidence: 99%

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Treprostinil Hydrogel Iontophoresis in Systemic Sclerosis‐Related Digital Skin Ulcers: A Safety Study

Guigui

Mazet

Blaise

et al. 2020

The Journal of Clinical Pharma

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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 0-4 h at 88 460% ± 6436% versus 12 730% ± 3397% baseline flux.min respectively; P < .001) and on the sole of the foot (AUC 0-3 h at 20 124% ± 6119% versus 3142% ± 3036% baseline flux.min, respectively; P = .018) with a trend on the finger. Among 5 patients with systemic sclerosis-related digital ulcer, 2 resolutive local adverse effects were reported. Iontophoresis of treprostinil hydrogel was safe in systemic sclerosis patients with digital ulcer.

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Section: Discussionsupporting

confidence: 72%

Section: Discussionmentioning

confidence: 99%