Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
The Effect of Gastric Acid Suppression with Esomeprazole on Treprostinil Diethanolamine Pharmacokinetics in Healthy Volunteers.
Rollins2, Kristan, Walker2, Susan, Kates2, Jennifer, Laliberte2, Kevin, Lim1, Allison
Treprostinil diethanolamine (TRE) is a prostacyclin analog currently being evaluated as a sustained release osmotic tablet for the treatment of digital ulcers in patients with systemic sclerosis (SSc). Esophageal manifestations of SSc are common requiring many patients to utilize acid suppressing therapies such as proton pump inhibitors (PPI). The use of acid suppressing therapies may alter the pharmacokinetics of concomitantly administered oral therapies via alterations in drug dissolution, absorption and metabolism. This study assessed the effect of steady-state esomeprazole induced gastric acid suppression on the pharmacokinetics of TRE.
This was a 9-day, single-center, open-label, single sequence study in which healthy volunteers were given a single dose of TRE SR 1 mg prior to and following repeated once daily oral dosing of esomeprazole 40 mg capsules over 7 days (Days 39). A single 1 mg oral dose of TRE was administered immediately following a 500 calorie meal on Days 1 and 8. Eighteen blood samples were obtained over 36 hours following each TRE dose. Plasma concentrations of treprostinil were quantified by liquid chromatography/mass spectrometry. Safety was assessed via adverse event reporting, clinical laboratories, physical exams, and ECGs.
Fifteen male and fifteen female healthy volunteers with a mean age of 34 years (range 2055 years) were enrolled. Concomitant administration of TRE and esomeprazole (test) following repeated esomeprazole dosing resulted in equivalent treprostinil exposure (Cmax and AUC) as compared to TRE dosing alone (reference) as described in Table 1. The most commonly reported adverse events included headache (8 subjects), flushing (2 subjects) and dizziness (2 subjects). There were no clinically significant treatment emergent changes in clinical laboratories, ECGs or vital signs.
Esomeprazole-induced gastric acid suppression had no impact on single dose TRE pharmacokinetics in healthy volunteers.
Table 1. Preliminary Treprostinil Pharmacokinetic Parameters
|Parameter||Least Squares Geometric Means||Ratio of Geometric Mean (Test/Reference)||90% Confidence Interval|
|Cmax (ng/mL)||0.84||0.84||1.00||(0.85, 1.17)|
|AUCinf (ng*hr/mL)||4.01||3.80||0.95||(0.87, 1.04)|
|AUClast (ng*hr/mL)||3.93||3.79||0.96||(0.89, 1.05)|
To cite this abstract, please use the following information:
Rollins, Kristan, Walker, Susan, Kates, Jennifer, Laliberte, Kevin, Lim, Allison; The Effect of Gastric Acid Suppression with Esomeprazole on Treprostinil Diethanolamine Pharmacokinetics in Healthy Volunteers. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :597