Abstract: In our previous study, a novel organic selenium compound Eb was synthesized and found to have significant antitumor activity with much less toxicity compared with the leading compound Ebselen. Unfortunately, Eb was practically insoluble in water (2.57 μg/mL) and had very low oral bioavailability, thus its clinical application was greatly limited. In the present study, the inclusion complex of Eb with 2-hydroxypropyl-β-cyclodextrin (HP-βCD) was prepared and pharmacokinetics of Eb and the inclusion complex were investigated. The water solubility of Eb was dramatically enhanced by inclusion with HP-βCD, which reached 8.4 mg/mL. The pharmacokinetic study showed that the elimination half-life (t1/2β) of Eb was between 22 h and 30 h and the distribution half-life (t1/2α) of Eb was 1 h. The results indicated that Eb was rapidly distributed to tissues but slowly eliminated in rats. The absolute bioavailability of Eb/HP-βCD inclusion complex solution through the oral route was 28.3%, and it was 1552% that of Eb in its pure form. In summary, the absorption of Eb in the Eb/HP-βCD inclusion complex was better and faster than that of Eb in its pure form.

Key words: Eb, Organoselenium, Hydroxypropyl-β-cyclodextrin, Inclusion complexes, Pharmacokinetics