INTRODUCTION: Treprostinil diethanolamine is an innovative salt form of the 
prostacyclin analogue, treprostinil sodium, developed as an oral sustained 
release (SR) osmotic tablet. The availability of a formulation permitting 
convenient systemic delivery might have applicability to scleroderma vascular 
complications. We evaluated pharmacokinetics and perfusion in scleroderma 
patients with digital ischemia following escalating twice-daily doses of 
treprostinil diethanolamine SR.
METHODS: Scleroderma patients with digital ulcers were enrolled in this 
dual-center, open-label, phase I pharmacokinetic study. Drug concentrations and 
perfusion, quantified by laser Doppler imaging, were measured over 12 hours at 
the 2 mg and 4 mg (or maximally tolerated) doses. Pharmacokinetic parameters 
were determined from individual plasma concentration versus time profiles using 
non-compartmental analysis methods. Digital perfusion and skin temperature were 
modeled as a function of log-transformed drug concentration and other covariates 
by performing repeated measures analyses using random effects models.
RESULTS: Nineteen scleroderma patients (84% female, 53% limited scleroderma) 
received treprostinil diethanolamine SR with dose titration up to 4 mg twice 
daily as tolerated. Peak concentrations (mean maximum plasma concentration 
(Cmax) = 1,176 and 2,107 pg/mL) occurred approximately 3.6 hours after dose 
administration, and overall exposure (under the plasma concentration-time curve 
from time 0 to 12 hours post dose (AUC0-12) = 7,187 and 12,992 hr*pg/mL) was 
linear between the 2 mg and 4 mg doses. Perfusion and digital skin temperature 
were positively associated with log-transformed plasma concentration at the 4 mg 
dose (P = 0.015 and P = 0.013, respectively). The most frequent adverse events 
were similar to those seen with prostacyclin analogues.
CONCLUSIONS: Oral treprostinil diethanolamine was effectively absorbed in 
patients with scleroderma. Drug administration was temporally associated with 
improved cutaneous perfusion and temperature. Treprostinil diethanolamine may 
provide a new therapeutic option for Raynaud's phenomenon and the peripheral 
vascular disease of scleroderma.
TRIAL REGISTRATION: ClinicalTrials.gov NCT00848939.