The Effect of a High‐Fat Meal on the Pharmacokinetics of Ixazomib, an Oral Proteasome Inhibitor, in Patients With Advanced Solid Tumors or Lymphoma. (17th March 2016)

• Record Type: Journal Article
• Authors: Gupta, Neeraj; Hanley, Michael J.; Venkatakrishnan, Karthik; Wang, Bingxia; Sharma, Sunil; Bessudo, Alberto; Hui, Ai‐Min; Nemunaitis, John
• Is Part Of: Journal of clinical pharmacology. Volume 56:Number 10(2016)
• Page Start: 1288
• Page End: 1295
• Publication Date: 2016-03-17
• Subjects: multiple myeloma -- ixazomib -- pharmacokinetics -- food effects; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Pharmacology, Clinical -- Periodicals; 615.1
• DOI: 10.1002/jcph.719
• Languages: English
• ISSNs: 0091-2700

Abstract

Abstract: Ixazomib is the first oral proteasome inhibitor to be investigated in the clinic. This clinical study assessed whether the pharmacokinetics of ixazomib would be altered if administered after a high‐calorie, high‐fat meal. In a 2‐period, 2‐sequence, crossover study design, adult patients with advanced solid tumors or lymphoma received a 4‐mg oral dose of ixazomib as immediate‐release capsules on day 1 without food (fasted, administered following an overnight fast) or with food (fed, following consumption of a high‐calorie, high‐fat meal), followed by another dose on day 15 in the alternate food intake condition (fasted to fed or fed to fasted). Twenty‐four patients were enrolled; of these, 15 were included in the pharmacokinetic‐evaluable population. Administration of ixazomib after a high‐fat meal reduced both the rate and extent of absorption of ixazomib. Under fed conditions, the median time to peak plasma concentration (Tmax ) of ixazomib was delayed by approximately 3 hours compared with administration in the fasted state (1.02 hours vs 4.0 hours), and there was a 28% reduction in total systemic exposure (area under the curve, AUC) and a 69% reduction in peak plasma concentration (Cmax ). Together, the results support the administration of ixazomib on an empty stomach, at least 1 hour before or at least 2 hours after food. These recommendations are reflected in the United States Prescribing Information for ixazomib (clinicaltrials.gov identifier NCT01454076).