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 study 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 micrograms/ml (mean +/- SD) at 5 hr and 0.25 +/- 0.15 mu/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.
Ueda
T
T
First Department of Internal Medicine, Fukui Medical School, Japan.
Tohyama
K
K
Wano
Y
Y
Tsutani
H
H
Fukushima
T
T
Iwasaki
H
H
Urasaki
Y
Y
Gotoh
N
N
Kimura
S
S
Okumura
E
E
D000328:Adult; D000368:Aged; D000753:Anemia, Refractory / Q000188:drug therapy; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007930:Leucine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy*; D010865:Pilot Projects
D007155:Immunologic Factors; D007930:Leucine; C012211:ubenimex