Absorption improvement of sepantronium bromide (YM155) by aminoalkyl methacrylate copolymers in in situ intestinal tracts of mice

作者：Ishii Takuya^*; Kobayashi Naoki; Maeda Atsushi; Kondo Hiromu; Sako Kazuhiro; Yamada Shizuo; Kagawa Yoshiyuki

来源：JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY, 2015, 27: 1-8.

DOI：10.1016/j.jddst.2015.03.002

• Sepantronium bromide (YM155)
• Aminoalkyl methacrylate copolymer (Eudragit (R) E)
• Absorption improvement
• Poorly absorbed compounds
• Oral formulation
• Mucin

Sepantronium bromide (YM155) is a small molecule suppressant of survivin with time-dependent antitumor activity. In Phase II trials, the dosage form is a parenteral solution for continuous intravenous administration for 7 days. Although an oral YM155 formulation is required to improve patient convenience, oral bioavailability is low due to poor membrane permeability. Plasma concentrations of YM155 were significantly increased in intestinal loops pre-washed with phosphate buffered saline (p < 0.05). In addition, plasma concentrations of YM155 significantly decreased in the presence of mucin, which is a typical anionic substance in the intestinal tract (p < 0.05). Freeze-dried powder of aminoalkyl methacrylate copolymer (Eudragit (R) E) with HCI (E-FD) improved YM155 absorption in mice. In addition, E-FD suppressed the interaction between YM155 and mucin. These results suggest that E-FD improves YM155 absorption by reducing the interaction between YM155 and mucin. E-FD is therefore a promising candidate as an absorption-improving agent for the development of oral formulations of YM155.

• 出版日期2015-6