We aimed to assess the bioavailability of eltrombopag PfOS relative to the tablet formulation and the effect of a high-calcium meal on PfOS bioavailability.
In this single-dose, open-label, randomized-sequence, crossover study, healthy subjects received 25 mg eltrombopag orally as a tablet fasted and as PfOS fasted or with, 2 hours before, or 2 hours after a high-calcium meal. Noncompartmental pharmacokinetic parameters were estimated from plasma concentration-time data collected over 72 hours post-dose. Tolerability was assessed by laboratory tests, physical examinations, and adverse events (AEs).
The 40 enrolled subjects included 22 males and 18 females of white/European (60%) or African-American/African (40%) heritage with mean (SD) (mininum, maximum) age of 34 (12) (19, 62) years, weight of 75 (12) (54, 101) kg, and body mass index of 25.8 (2.9) (19.7, 30) kg/m2. Plasma eltrombopag AUC0-鈭?/sub> was higher for the PfOS than the tablet (geometric least-squares mean ratio [GMR]: 1.22; 90%CI: 1.08-1.38). Plasma eltrombopag AUC0-鈭?/sub> was reduced when the PfOS was administered with a high-calcium meal (GMR: 0.25; 90%CI: 0.224-0.287) or 2 hours after a meal (GMR: 0.53; 90%CI: 0.470-0.601), and, to a lesser extent, when administered 2 hours before a meal (GMR: 0.80; 90%CI: 0.711-0.908). The absorption lag time and t陆 did not differ between treatments; Tmax was delayed 1 hour when the PfOS was dosed with a high-calcium meal. AEs were not serious and mild or moderate in intensity. AEs reported in >1 subject included headache (11 subjects; 27.5%), presyncope (3 subjects, 7.5%), and vomiting (2 subjects, 5%). No clinically significant trends in laboratory tests or vital signs were observed. In a healthy adult volunteer population, bioavailability of eltrombopag PfOS was greater than the tablet and was reduced when administered with or 2 hours before or after a high-calcium meal; this effect was attenuated with PfOS dosing 2 hours before the meal. Eltrombopag was generally well tolerated. Identifier: .Conclusions