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The effect of different meal compositions on the oral bioavailability of treprostinil diolamine in healthy volunteers
Author(s) -
Lim A.,
WangSmith L.,
Kates J.,
Laurent A.,
Kumar P.,
Laliberte K.
Publication year - 2013
Publication title -
journal of clinical pharmacy and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.622
H-Index - 73
eISSN - 1365-2710
pISSN - 0269-4727
DOI - 10.1111/jcpt.12085
Subject(s) - treprostinil , meal , medicine , bioavailability , crossover study , calorie , oral administration , adverse effect , pharmacology , pulmonary hypertension , alternative medicine , pathology , placebo
Summary 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 ( WB 500), a 250‐calorie well‐balanced meal ( WB 250), a 250‐calorie high‐fat meal ( HF 250) 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 ( C max and AUC 0‐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.