Effects of dacomitinib on the pharmacokinetics of poziotinib in vivo and in vitro

Dacomitinib and poziotinib, irreversible ErbB family blockers, are often used for treatment of non-small cell lung cancer (NSCLC) in the clinic. This study investigates the effect of dacomitinib on the pharmacokinetics of poziotinib in rats. Twelve Sprague-Dawley rats were randomly divided into two...

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Bibliographic Details
Published in:Pharmaceutical biology 2021-12, Vol.59 (1), p.455-462
Main Authors: Ji, Weiping, Shen, Jiquan, Wang, Bo, Chen, Feifei, Meng, Deru, Wang, Shuanghu, Dai, Dapeng, Zhou, Yunfang, Wang, Changxiong, Zhou, Quan
Format: Article
Language:English
Subjects:
Administration, Oral
Animals
Antineoplastic Agents - administration & dosage
Antineoplastic Agents - pharmacokinetics
Antineoplastic Agents - pharmacology
Area Under Curve
Chromatography, High Pressure Liquid
CYP2D6 protein
Cytochrome P450
Drug dosages
Drug interaction
Drug Interactions
drug-drug interaction
ErbB protein
Humans
Inhibitory Concentration 50
Liver
Lung cancer
Microsomes
Microsomes, Liver - metabolism
Non-small cell lung carcinoma
Oral administration
Pharmacokinetics
Quinazolines - administration & dosage
Quinazolines - pharmacokinetics
Quinazolinones - administration & dosage
Quinazolinones - pharmacology
Rats
Rats, Sprague-Dawley
Small cell lung carcinoma
Tandem Mass Spectrometry
Tyrosine kinase inhibitor
UPLC-MS/MS
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Summary:Dacomitinib and poziotinib, irreversible ErbB family blockers, are often used for treatment of non-small cell lung cancer (NSCLC) in the clinic. This study investigates the effect of dacomitinib on the pharmacokinetics of poziotinib in rats. Twelve Sprague-Dawley rats were randomly divided into two groups: the test group (20 mg/kg dacomitinib for 14 consecutive days) and the control group (equal amounts of vehicle). Each group was given an oral dose of 10 mg/kg poziotinib 30 min after administration of dacomitinib or vehicle at the end of the 14 day administration. The concentration of poziotinib in plasma was quantified by UPLC-MS/MS. Both in vitro effects of dacomitinib on poziotinib and the mechanism of the observed inhibition were studied in rat liver microsomes and human liver microsomes. When orally administered, dacomitinib increased the AUC, T max and decreased CL of poziotinib (p 
ISSN:1388-0209
1744-5116
DOI:10.1080/13880209.2021.1914114