WHAT IS KNOWN: Treprostinil diolamine (oral treprostinil) is a prostacyclin 
analogue currently being evaluated for the treatment of pulmonary arterial 
hypertension as a sustained-release (SR) oral tablet. Previous data have 
demonstrated that the oral bioavailability of treprostinil was improved when 
taken with a meal containing at least 500 calories.
OBJECTIVE: As twice-daily intake of a high-fat, high-calorie meal may be 
undesirable or not feasible for some patients, this open-label, randomized, 
crossover study evaluated the effect of different meal compositions [a 
500-calorie well-balanced meal (WB500), a 250-calorie well-balanced meal 
(WB250), a 250-calorie high-fat meal (HF250) and a 250-calorie well-balanced 
liquid meal (Ensure®)] on the relative bioavailability of oral treprostinil.
METHODS: Thirty-two healthy volunteers were administered a single 1-mg SR tablet 
of oral treprostinil immediately following each study meal. Each dose of oral 
treprostinil was separated by a 7-day washout period. Serial plasma samples were 
obtained over a 36-h postdose. Safety was assessed in all patients who received 
study drug.
RESULTS AND DISCUSSION: Treprostinil plasma exposure (Cmax and AUC0-inf) 
decreased only slightly, 5-15% with decreasing caloric and increasing fat 
content. Headache was the most commonly reported prostacyclin-related adverse 
event (three reports).
WHAT IS NEW AND CONCLUSION: Overall, there were no clinically significant 
differences in the relative bioavailability of oral treprostinil when 
administered immediately after meals containing 250-500 calories and 30-50% fat. 
These data support the administration of oral treprostinil with a meal 
containing as few as 250 calories and 30-50% fat, which is significant for 
ensuring patient convenience and compliance, particularly as consistency with 
regard to meals may impact oral treprostinil pharmacokinetics.