PMID- 29471066
OWN - NLM
STAT- MEDLINE
DCOM- 20180912
LR  - 20200106
IS  - 2299-5684 (Electronic)
IS  - 1734-1140 (Linking)
VI  - 70
IP  - 2
DP  - 2018 Apr
TI  - A pharmacokinetic study on lapatinib in type 2 diabetic rats.
PG  - 191-195
LID - S1734-1140(17)30311-0 [pii]
LID - 10.1016/j.pharep.2017.09.003 [doi]
AB  - BACKGROUND: Diabetes mellitus (DM) is a complex metabolic disorder which affects 
      the function of numerous tissues and alters the pharmacokinetic parameters of 
      many drugs. As many oncological patients are diabetics, it is important to 
      determine the influence of this chronic disease on the pharmacokinetics (PK) of 
      anticancer drugs. Lapatinib is a tyrosine kinase inhibitor (TKI), approved for 
      the treatment of human epidermal growth factor receptor 2 (HER2)-positive 
      metastatic breast cancer. The aim of the study was to compare the PK of lapatinib 
      in normal and type 2 diabetes mellitus (T2DM) model rats. Additionally, the 
      effect of lapatinib on blood glucose concentrations was examined. METHODS: The PK 
      of lapatinib was studied in healthy rats (n=6, the healthy group) and T2DM model 
      rats (n=6, the diabetic group). The rats received lapatinib orally as a single 
      dose of 50mg. Plasma concentrations of lapatinib were measured with 
      high-performance liquid chromatography method coupled with a tandem mass 
      spectrometry. RESULTS: The plasma concentrations of lapatinib were increased in 
      the T2DM model rats. There were statistically significant differences between the 
      groups in C(max) (p=0.0104) and AUC(0-t) (p=0.0265). The reduction of glycaemia 
      in the range of 1.2-41.5% and in the range of 4.1-36.8% was observed in the 
      diabetic and healthy animals, respectively. CONCLUSIONS: Higher concentrations of 
      lapatinib in the diabetic rats may suggest the need for application of lower 
      doses of this TKI in patients with DM.
CI  - Copyright (c) 2017. Published by Elsevier B.V.
FAU - Karbownik, Agnieszka
AU  - Karbownik A
AD  - Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical 
      Sciences, Poznan, Poland. Electronic address: agnieszkakarbownik@o2.pl.
FAU - Szalek, Edyta
AU  - Szalek E
AD  - Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical 
      Sciences, Poznan, Poland.
FAU - Sobanska, Katarzyna
AU  - Sobanska K
AD  - Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical 
      Sciences, Poznan, Poland.
FAU - Klupczynska, Agnieszka
AU  - Klupczynska A
AD  - Department of Inorganic and Analytical Chemistry, Poznan University of Medical 
      Sciences, Poznan, Poland.
FAU - Plewa, Szymon
AU  - Plewa S
AD  - Department of Inorganic and Analytical Chemistry, Poznan University of Medical 
      Sciences, Poznan, Poland.
FAU - Grabowski, Tomasz
AU  - Grabowski T
AD  - Polpharma Biologics, Gdansk, Poland.
FAU - Wolc, Anna
AU  - Wolc A
AD  - Department of Animal Science, Iowa State University, Ames, IA, USA; Hy-Line 
      International, Dallas Center, IA USA.
FAU - Moch, Marta
AU  - Moch M
AD  - Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical 
      Sciences, Poznan, Poland.
FAU - Kokot, Zenon J
AU  - Kokot ZJ
AD  - Department of Inorganic and Analytical Chemistry, Poznan University of Medical 
      Sciences, Poznan, Poland.
FAU - Grzeskowiak, Edmund
AU  - Grzeskowiak E
AD  - Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical 
      Sciences, Poznan, Poland.
LA  - eng
PT  - Journal Article
DEP - 20170918
PL  - Switzerland
TA  - Pharmacol Rep
JT  - Pharmacological reports : PR
JID - 101234999
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Blood Glucose)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Quinazolines)
RN  - 0VUA21238F (Lapatinib)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/pharmacokinetics
MH  - Blood Glucose/drug effects
MH  - Chromatography, High Pressure Liquid/methods
MH  - Diabetes Mellitus, Experimental/*blood
MH  - Diabetes Mellitus, Type 2/*blood
MH  - Lapatinib
MH  - Male
MH  - Protein Kinase Inhibitors/pharmacokinetics
MH  - Quinazolines/blood/*pharmacokinetics
MH  - Rats
MH  - Rats, Wistar
MH  - Tandem Mass Spectrometry/methods
OTO - NOTNLM
OT  - Diabetic rats
OT  - Glycaemia
OT  - Lapatinib
OT  - Pharmacokinetics
EDAT- 2018/02/23 06:00
MHDA- 2018/09/13 06:00
CRDT- 2018/02/23 06:00
PHST- 2017/04/28 00:00 [received]
PHST- 2017/07/31 00:00 [revised]
PHST- 2017/09/15 00:00 [accepted]
PHST- 2018/02/23 06:00 [pubmed]
PHST- 2018/09/13 06:00 [medline]
PHST- 2018/02/23 06:00 [entrez]
AID - S1734-1140(17)30311-0 [pii]
AID - 10.1016/j.pharep.2017.09.003 [doi]
PST - ppublish
SO  - Pharmacol Rep. 2018 Apr;70(2):191-195. doi: 10.1016/j.pharep.2017.09.003. Epub 
      2017 Sep 18.