PMID- 27196567
OWN - NLM
STAT- MEDLINE
DCOM- 20170606
LR  - 20231104
IS  - 1365-2141 (Electronic)
IS  - 0007-1048 (Print)
IS  - 0007-1048 (Linking)
VI  - 174
IP  - 5
DP  - 2016 Sep
TI  - A pharmacokinetics and safety phase 1/1b study of oral ixazomib in patients with 
      multiple myeloma and severe renal impairment or end-stage renal disease requiring 
      haemodialysis.
PG  - 748-59
LID - 10.1111/bjh.14125 [doi]
AB  - Renal impairment (RI) is a major complication of multiple myeloma (MM). This 
      study aimed to characterize the single-dose pharmacokinetics (PK) of the oral 
      proteasome inhibitor, ixazomib, in cancer patients with normal renal function 
      [creatinine clearance (CrCl) >/=90 ml/min; n = 20), severe RI (CrCl <30 ml/min; 
      n = 14), or end-stage renal disease requiring haemodialysis (ESRD; n = 7). PK and 
      adverse events (AEs) were assessed after a single 3 mg dose of ixazomib. Ixazomib 
      was highly bound to plasma proteins (~99%) in all renal function groups. Unbound 
      and total systemic exposures of ixazomib were 38% and 39% higher, respectively, 
      in severe RI/ESRD patients versus patients with normal renal function. Total 
      ixazomib concentrations were similar in pre- and post-dialyser samples collected 
      from ESRD patients; therefore, ixazomib can be administered without regard to 
      haemodialysis timing. Except for anaemia, the incidence of the most common AEs 
      was generally similar across groups, but grade 3 and 4 AEs were more frequent in 
      the severe RI/ESRD groups versus the normal group (79%/57% vs. 45%), as were 
      serious AEs (43%/43% vs. 15%). The PK and safety results support a reduced 
      ixazomib dose of 3 mg in patients with severe RI/ESRD.
CI  - (c) 2016 The Authors. British Journal of Haematology published by John Wiley & Sons 
      Ltd.
FAU - Gupta, Neeraj
AU  - Gupta N
AD  - Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda 
      Pharmaceutical Company Limited, Cambridge, MA, USA.
FAU - Hanley, Michael J
AU  - Hanley MJ
AD  - Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda 
      Pharmaceutical Company Limited, Cambridge, MA, USA.
FAU - Harvey, R Donald
AU  - Harvey RD
AD  - Winship Cancer Institute of Emory University, Atlanta, GA, USA.
FAU - Badros, Ashraf
AU  - Badros A
AD  - University of Maryland, Baltimore, MD, USA.
FAU - Lipe, Brea
AU  - Lipe B
AD  - University of Kansas Clinical Research Center, Fairway, KS, USA.
FAU - Kukreti, Vishal
AU  - Kukreti V
AD  - University Health Network, Toronto, ON, Canada.
FAU - Berdeja, Jesus
AU  - Berdeja J
AD  - Sarah Cannon Cancer Center, Nashville, TN, USA.
FAU - Yang, Huyuan
AU  - Yang H
AD  - Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda 
      Pharmaceutical Company Limited, Cambridge, MA, USA.
FAU - Hui, Ai-Min
AU  - Hui AM
AD  - Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda 
      Pharmaceutical Company Limited, Cambridge, MA, USA.
FAU - Qian, Mark
AU  - Qian M
AD  - Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda 
      Pharmaceutical Company Limited, Cambridge, MA, USA.
FAU - Zhang, Xiaoquan
AU  - Zhang X
AD  - Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda 
      Pharmaceutical Company Limited, Cambridge, MA, USA.
FAU - Venkatakrishnan, Karthik
AU  - Venkatakrishnan K
AD  - Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda 
      Pharmaceutical Company Limited, Cambridge, MA, USA.
FAU - Chari, Ajai
AU  - Chari A
AD  - Mount Sinai Medical Center, New York, NY, USA.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
DEP - 20160516
PL  - England
TA  - Br J Haematol
JT  - British journal of haematology
JID - 0372544
RN  - 0 (Blood Proteins)
RN  - 0 (Boron Compounds)
RN  - 0 (Protease Inhibitors)
RN  - 71050168A2 (ixazomib)
RN  - TE7660XO1C (Glycine)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Anemia/etiology
MH  - Blood Proteins/metabolism
MH  - Boron Compounds/administration & dosage/metabolism/*pharmacokinetics
MH  - Drug Dosage Calculations
MH  - Female
MH  - Glycine/administration & dosage/*analogs & 
      derivatives/metabolism/pharmacokinetics
MH  - Humans
MH  - Kidney Failure, Chronic/therapy
MH  - Male
MH  - Middle Aged
MH  - Multiple Myeloma/complications/*drug therapy
MH  - Protease Inhibitors/administration & dosage/*pharmacokinetics
MH  - Renal Dialysis
MH  - Renal Insufficiency/*therapy
PMC - PMC5084759
OTO - NOTNLM
OT  - dialysis
OT  - ixazomib
OT  - multiple myeloma
OT  - pharmacokinetics
OT  - renal impairment
EDAT- 2016/05/20 06:00
MHDA- 2017/06/07 06:00
PMCR- 2016/10/28
CRDT- 2016/05/20 06:00
PHST- 2016/02/10 00:00 [received]
PHST- 2016/03/09 00:00 [accepted]
PHST- 2016/05/20 06:00 [entrez]
PHST- 2016/05/20 06:00 [pubmed]
PHST- 2017/06/07 06:00 [medline]
PHST- 2016/10/28 00:00 [pmc-release]
AID - BJH14125 [pii]
AID - 10.1111/bjh.14125 [doi]
PST - ppublish
SO  - Br J Haematol. 2016 Sep;174(5):748-59. doi: 10.1111/bjh.14125. Epub 2016 May 16.