Plasma protein binding is 99%.The substance is metabolized by many CYP enzymes (percentages in vitro, at higher than clinical concentrations: CYP3A4 42.3%, CYP1A2 26.1%, CYP2B6 16.0%, CYP2C8 6.0%, CYP2D6 4.8%, CYP2C9 4.8%, CYP2C9 <1%) as well as non-CYP enzymes, which could explain the low interaction potential. Clearance is about 1.86 litres per hour with a wide variability of 44% between individuals, and plasma half-life is 9.5 days. 62% of ixazomib and its metabolites are excreted via the urine (of which less than 3.5% in unchanged form) and 22% via the faeces. Chemistry
Ixazomib is a boronic acid and peptide analogue like the older bortezomib. It contains a derivative  of the amino acid leucine with the carboxylic acid group being replaced by a boronic acid; and the remainder of the molecule has been likened to phenylalanine. The structure has been found through a large-scale screening of boron-containing molecules. History
The drug was developed by Takeda. It got US and European orphan drug status for multiple myeloma in 2011, and for AL amyloidosis in 2012. Takeda submitted a US new drug application for multiple myeloma in July 2015. In September 2015, the U.S. Food and Drug Administration (FDA) granted ixazomib combined with lenalidomide and dexamethasone a priority review designation for multiple myeloma. On 20 November 2015, the FDA approved this combination for second-line treatment.The request for marketing authorisation in Europe was initially refused by the European Medicines Agency (EMA) in May 2016 due to insufficient data showing a benefit of treatment.
After Takeda requested a re-examination, the EMA granted a marketing authorisation on 21 November 2016 on the condition that further efficacy studies be conducted. The approval indication is the same as in the US. Research
As of January 2017, ixazomib is also in Phase III clinical trials for the treatment of AL amyloidosis and plasmacytoma of the bones, and in Phase I/II trials for various other conditions. References
External links
"Ixazomib". Drug Information Portal. U.S. National Library of Medicine. "Ixazomib citrate". Drug Information Portal. U.S. National Library of Medicine.