The effect of different meal compositions on the oral bioavailability of treprostinil diolamine in healthy volunteers.

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.