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Microdose Study on Three Aromatase Inhibitors

Time

Wed, Jun 26 11:45AM
W 08

Title

Microdose Study on Three Aromatase Inhibitors

Abstract Summary

The study was jointly made by the Osaka City University Hospital and Riken of Japan from 2011 through 2012. Test substances (TMD-322, cetrozole, and anastrozole) were either synthesized or obtained from the outer sources. Oral and intravenous dosage forms of the compounds were prepared according to Japan's "GMP for Clinical Trial Substances" within the research facilities. An extended single-dose toxicity study was made for TMD-322 and cetrozole in Crl:CD(SD) rats according to ICH M3 guidelines. A cross-over design with a cassette dose mixture was employed in the clinical study. Six healthy male volunteers (age: 20 - 40)were randomly divided into two groups, to which were the oral and intravenous mixtures were administered in a cross-over scheme; one group receiving p.o. mixture and then i.v., and the other group receiving i.v.,. and then p.o., with an interval of 21 days. The amounts of the drugs in the mixture was determined according to the "Guidance on microdose clinical studies" issued in 2008 from Japan's Ministry of Health, labour and Welfare; one hundredth of the minimum effective dose (in this case, 10 micrograms). At a total of 12 (p.o.) and 14 (i.v.) time points within 3 days of the administration, blood samples were drawn from the subjects and the plasma concentration of the substances were measured with LC-MS. Consultation with Pharmaceuticals and Medical Devices Agency (PMDA) was held to seek advice on the overall study design and especially the dosing.

Poster Presenter

Toshiyoshi Tominaga
PhD,
Associate Executive Director for International Programs,
Pharmaceuticals and Medical Devices Agency (PMDA)
Japan

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