Disposition of a new tamibarotene prodrug in mice.

Abstract

Recently, a new compound IT-M-07000 was designed as a prodrug of tamibarotene, one of the therapeutic agents for acute promyelocytic leukemia. In the present study, IT-M-07000 was administered to mice to investigate whether it is actually metabolized to tamibarotene. Its metabolic pathway and the utility as a tamibarotene prodrug were also evaluated. After oral administration of IT-M-07000, IT-M-07000, tamibarotene and two compounds that were supposed to be metabolic intermediates in a beta-oxidation pathway of IT-M-07000 to tamibarotene were detected in mouse plasma. It was thus shown that IT-M-07000 is probably beta-oxidized to tamibarotene in mice. Comparison of tamibarotene concentration profiles after oral administration of IT-M-07000 or tamibarotene showed that the plasma tamibarotene concentration increased slower and was retained stable, and the area under the plasma concentration-time curve (AUC) of tamibarotene was larger in mice administered IT-M-07000 than tamibarotene. These results indicate that IT-M-07000 is possibly useful as a prodrug of tamibarotene.

• Authors: Megumi Sugitani, Rieko Abe, Nobutomo Ikarashi, Kiyomi Ito, Hideaki Muratake, Koichi Shudo, Kiyoshi Sugiyama
• Journal: Biological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 32 Issue 12 Pg. 1997-2001 (Dec 2009) ISSN: 1347-5215 [Electronic] Japan
• PMID: 19952418 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Benzoates
• IT-M-07000
• Phenylpropionates
• Prodrugs
• Tetrahydronaphthalenes
• tamibarotene

Topics

• Animals
• Antineoplastic Agents (blood, metabolism)
• Area Under Curve
• Benzoates (blood, metabolism)
• Male
• Metabolic Networks and Pathways
• Mice
• Phenylpropionates (metabolism)
• Prodrugs (metabolism)
• Tetrahydronaphthalenes (blood, metabolism)