Pharmacokinetic and clinical pilot study of high-dose intermittent ubenimex treatment in patients with myelodysplastic syndrome

Ubenimex is an orally active aminopeptidase inhibitor with an immunomodulating action. A pharmacokinetic and clinical pilot sandy of high-dose intermittent ubenimex was performed in patients with myelodysplastic syndrome. Ubenimex (150 mg/body) was administered orally, twice per day (at a 3 hr interval), twice a week, for at least 8 weeks. The concentrations of ubenimex and p-OH ubenimex, another active metabolite, increased gradually up to 7.1±4.7 μg/ml (mean±SD) at 5 hr and 0.25±0.15 μ/ml at 6 hr. The low percentage (4.2%) of the AUC ratio (p-OH ubenimex/ubenimex) suggested minimal metabolism. The plasma half-life of ubenimex was 2.1±0.7 hr and the total urinary recovery of both was 71.4% in 48 hr. Among 8 patients clinically studied, one achieved good response and another achieved minor response. These findings suggested good bioavailability, and a certain effectiveness of ubenimex in this administration method, which was worth trying, at least in restricted cases, such as cases with refractory disease or with a poor performance status