Metabolism and disposition of eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist, in healthy human subjects.

The metabolism and disposition of eltrombopag, the first-in-class small molecule human thrombopoietin receptor agonist, were studied in six healthy men after a single oral administration of a solution dose of [(14)C]eltrombopag (75 mg, 100 μCi). Eltrombopag was well tolerated. The drug was quickly absorbed and was the predominant circulating component in plasma (accounting for 63% of the total plasma radioactivity).

A rapid method for quantitatively estimating metabolites in human plasma in the absence of synthetic standards using a combination of liquid chromatography/mass spectrometry and radiometric detection.

An approach to estimating the levels of drug-related metabolites in human plasma in the absence of synthesized chemical standards has been developed. High-performance liquid chromatography/mass spectrometry (LC/MS) in combination with radiometric detection was used in this method. Biologically derived [(14)C] metabolites from preclinical in vitro and in vivo matrices are used as [(14)C] metabolite standards and their concentrations in matrices are calculated based on the corresponding radioactivity.