PMID- 25821156
OWN - NLM
STAT- MEDLINE
DCOM- 20160331
LR  - 20150707
IS  - 1552-4604 (Electronic)
IS  - 0091-2700 (Linking)
VI  - 55
IP  - 8
DP  - 2015 Aug
TI  - The pharmacokinetics and safety of idelalisib in subjects with moderate or severe 
      hepatic impairment.
PG  - 944-52
LID - 10.1002/jcph.504 [doi]
AB  - Idelalisib, a phosphatidylinositol 3-kinase delta (PI3Kdelta) inhibitor, is 
      metabolized primarily by aldehyde oxidase to form GS-563117, an inactive 
      metabolite, and is metabolized to a lesser extent by cytochrome P450 3A and 
      uridine 5'-diphospho-glucuronosyltransferase 1A4. In a mass balance study, the 
      orally administered idelalisib dose was recovered mainly in feces ( approximately 78%). This 
      study evaluated the pharmacokinetics and safety of a single 150-mg dose of 
      idelalisib in subjects with moderate or severe hepatic impairment and in age-, 
      sex-, and weight-matched, healthy controls. The idelalisib maximum observed 
      plasma concentration was generally comparable in subjects with moderate or severe 
      hepatic impairment versus healthy controls, whereas the mean area under the curve 
      was higher (58% to 59%). GS-563117 exposures were lower in impaired versus 
      healthy control subjects, likely because of lower formation in the setting of 
      liver impairment. Exploratory analyses indicated no relevant relationships 
      between idelalisib or GS-563117 plasma exposures and Child-Pugh-Turcotte scores. 
      Single oral doses of idelalisib 150 mg were well tolerated, with most 
      treatment-emergent adverse events (AEs) and laboratory abnormalities being grades 
      1 or 2 in severity. As such, no dose adjustment was required when initiating 
      idelalisib treatment in patients with mild or moderate hepatic impairment, 
      although close monitoring for potential AEs is recommended.
CI  - (c) 2015, The American College of Clinical Pharmacology.
FAU - Jin, Feng
AU  - Jin F
AD  - Gilead Sciences, Inc., Foster City, CA, USA.
FAU - Robeson, Michelle
AU  - Robeson M
AD  - Gilead Sciences, Inc., Seattle, WA, USA.
FAU - Zhou, Huafeng
AU  - Zhou H
AD  - Gilead Sciences, Inc., Seattle, WA, USA.
FAU - Hisoire, Grace
AU  - Hisoire G
AD  - Gilead Sciences, Inc., Foster City, CA, USA.
FAU - Ramanathan, Srini
AU  - Ramanathan S
AD  - Gilead Sciences, Inc., Foster City, CA, USA.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150527
PL  - England
TA  - J Clin Pharmacol
JT  - Journal of clinical pharmacology
JID - 0366372
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Purines)
RN  - 0 (Quinazolinones)
RN  - YG57I8T5M0 (idelalisib)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antineoplastic Agents/adverse effects/*pharmacokinetics
MH  - Female
MH  - Humans
MH  - Liver Diseases/*metabolism
MH  - Male
MH  - Middle Aged
MH  - Protein Binding
MH  - Protein Kinase Inhibitors/adverse effects/*pharmacokinetics
MH  - Purines/adverse effects/*pharmacokinetics
MH  - Quinazolinones/adverse effects/*pharmacokinetics
OTO - NOTNLM
OT  - PI3Kdelta
OT  - hepatic impairment
OT  - idelalisib
OT  - pharmacokinetics
OT  - safety
EDAT- 2015/03/31 06:00
MHDA- 2016/04/01 06:00
CRDT- 2015/03/31 06:00
PHST- 2014/12/19 00:00 [received]
PHST- 2015/03/24 00:00 [accepted]
PHST- 2015/03/31 06:00 [entrez]
PHST- 2015/03/31 06:00 [pubmed]
PHST- 2016/04/01 06:00 [medline]
AID - 10.1002/jcph.504 [doi]
PST - ppublish
SO  - J Clin Pharmacol. 2015 Aug;55(8):944-52. doi: 10.1002/jcph.504. Epub 2015 May 27.