The effect of different meal compositions on the oral bioavailability of
treprostinil diolamine in healthy volunteers.
Author(s): Lim A(1), Wang-Smith L, Kates J, Laurent A, Kumar P, Laliberte K.
Affiliation(s): Author information:
(1)United Therapeutics, Research Triangle Park, NC.
Publication date & source: 2013, J Clin Pharm Ther. , 38(6):450-5
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
(EnsureĀ®)] 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.
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