PMID- 33108009
OWN - NLM
STAT- MEDLINE
DCOM- 20211026
LR  - 20220114
IS  - 1365-2710 (Electronic)
IS  - 0269-4727 (Linking)
VI  - 46
IP  - 2
DP  - 2021 Apr
TI  - Effects of proprotein convertase subtilisin/kexin type 9 and nilotinib plasma 
      concentrations on nilotinib-induced hypercholesterolaemia in patients with 
      chronic myeloid leukaemia.
PG  - 382-387
LID - 10.1111/jcpt.13294 [doi]
AB  - WHAT IS KNOWN AND OBJECTIVE: The purpose of this study was to investigate the 
      relationships among nilotinib plasma trough concentration (C(0) ), low-density 
      lipoprotein (LDL) cholesterol, and PCSK9 plasma concentration in 31 patients with 
      chronic myeloid leukaemia. METHODS: Plasma concentrations of nilotinib and PCSK9 
      were measured by high-performance liquid chromatography and enzyme-linked 
      immunosorbent assays, respectively. RESULTS AND DISCUSSION: LDL cholesterol 
      concentrations at 1 month after nilotinib treatment were significantly increased 
      compared with those before therapy. The mean C(0) (+/-SD) of nilotinib at 1, 2, and 
      3 months after nilotinib treatment were 645 +/- 516, 902 +/- 623, and 
      951 +/- 1088 ng/mL, respectively. Mean PCSK9 concentrations at 3 months after 
      nilotinib treatment were significantly higher than those at the start of therapy 
      (320 vs 257 ng/mL, respectively, P = .019). When the change rate in the PCSK9 
      concentration induced by nilotinib was classified with a cut-off value of +40%, 
      the change rate in LDL cholesterol in patients with a change rate in PCSK9 of 
      >/=40% was significantly higher than that in patients with a PCSK9 change rate of 
      <40% (67.1% vs 38.0%, P = .043); however, there were no differences in mean 
      nilotinib C(0) . WHAT IS NEW AND CONCLUSION: Nilotinib may lead to 
      hypercholesterolaemia by increasing plasma concentrations of PCSK9 after indirect 
      inhibition of mammalian target of rapamycin (mTOR) complex 1. In addition, 
      certain patients seem to have high sensitivity for nilotinib in a signalling 
      cascade of the PI3K/Akt/mTOR pathway, despite low plasma concentrations of 
      nilotinib. Consequently, nilotinib-induced hypercholesterolaemia could not be 
      predicted based on the plasma concentration of nilotinib.
CI  - (c) 2020 John Wiley & Sons Ltd.
FAU - Abumiya, Maiko
AU  - Abumiya M
AD  - Department of Pharmacy, Akita University Hospital, Akita, Japan.
FAU - Akamine, Yumiko
AU  - Akamine Y
AUID- ORCID: 0000-0002-1346-757X
AD  - Department of Pharmacy, Akita University Hospital, Akita, Japan.
FAU - Sato, Shiori
AU  - Sato S
AD  - Department of Pharmacy, Akita University Hospital, Akita, Japan.
FAU - Takahashi, Saori
AU  - Takahashi S
AD  - Department of Hematology, Nephrology, and Rheumatology, Akita University Graduate 
      School of Medicine, Akita, Japan.
AD  - Clinical Research Promotion and Support Center, Akita University Hospital, Akita, 
      Japan.
FAU - Yoshioka, Tomoko
AU  - Yoshioka T
AD  - Department of Hematology, Nephrology, and Rheumatology, Akita University Graduate 
      School of Medicine, Akita, Japan.
FAU - Kameoka, Yoshihiro
AU  - Kameoka Y
AD  - Department of Hematology, Nephrology, and Rheumatology, Akita University Graduate 
      School of Medicine, Akita, Japan.
AD  - Clinical Research Promotion and Support Center, Akita University Hospital, Akita, 
      Japan.
FAU - Takahashi, Naoto
AU  - Takahashi N
AUID- ORCID: 0000-0002-6758-3787
AD  - Department of Hematology, Nephrology, and Rheumatology, Akita University Graduate 
      School of Medicine, Akita, Japan.
FAU - Miura, Masatomo
AU  - Miura M
AUID- ORCID: 0000-0001-7120-2425
AD  - Department of Pharmacy, Akita University Hospital, Akita, Japan.
LA  - eng
GR  - 20K07150/Japan Society for the Promotion of Science/
PT  - Journal Article
DEP - 20201027
PL  - England
TA  - J Clin Pharm Ther
JT  - Journal of clinical pharmacy and therapeutics
JID - 8704308
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Cholesterol, LDL)
RN  - 0 (Pyrimidines)
RN  - EC 3.4.21.- (Proprotein Convertase 9)
RN  - F41401512X (nilotinib)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antineoplastic Agents/*adverse effects/therapeutic use
MH  - Cholesterol, LDL/drug effects
MH  - Chromatography, High Pressure Liquid
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Humans
MH  - Hypercholesterolemia/*chemically induced
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*drug therapy
MH  - Male
MH  - Middle Aged
MH  - Proprotein Convertase 9/*blood
MH  - Pyrimidines/*adverse effects/blood/therapeutic use
MH  - Retrospective Studies
OTO - NOTNLM
OT  - low-density lipoprotein cholesterol
OT  - nilotinib
OT  - plasma trough concentration
OT  - proprotein convertase subtilisin/kexin type 9
EDAT- 2020/10/28 06:00
MHDA- 2021/10/27 06:00
CRDT- 2020/10/27 12:14
PHST- 2020/09/24 00:00 [revised]
PHST- 2020/07/21 00:00 [received]
PHST- 2020/09/28 00:00 [accepted]
PHST- 2020/10/28 06:00 [pubmed]
PHST- 2021/10/27 06:00 [medline]
PHST- 2020/10/27 12:14 [entrez]
AID - 10.1111/jcpt.13294 [doi]
PST - ppublish
SO  - J Clin Pharm Ther. 2021 Apr;46(2):382-387. doi: 10.1111/jcpt.13294. Epub 2020 Oct 
      27.