This study aimed to investigate the interactions between icotinib/apatinib and oxycodone in rats and to unveil the underlying mechanism. An ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated to determine oxycodone and its demethylated metabolite simultaneously. , Sprague-Dawley (SD) male rats were administered oxycodone with or without icotinib or apatinib. Blood samples were collected and subjected to UPLC-MS/MS analysis. An enzyme incubation assay was performed to investigate the mechanism of drug-drug interaction using both rat and human liver microsomes (RLM and HLM). The results showed that icotinib markedly increased the AUC and AUC of oxycodone but decreased the CL. The C of oxycodone increased significantly upon co-administration of apatinib. , the K value of oxycodone metabolism was 101.7 ± 5.40 μM and 529.6 ± 19.60 μM in RLMs and HLMs, respectively. Icotinib and apatinib inhibited the disposition of oxycodone, with a mixed mechanism in RLM (IC = 3.29 ± 0.090 μM and 0.95 ± 0.88 μM, respectively) and a competitive and mixed mechanism in HLM (IC = 22.34 ± 0.81 μM and 0.48 ± 0.05 μM, respectively). In conclusion, both icotinib and apatinib inhibit the metabolism of oxycodone and . Therefore, the dose of oxycodone should be reconsidered when co-administered with icotinib or apatinib.
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| http://dx.doi.org/10.7717/peerj.16601 | DOI Listing |
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This study aimed to investigate the interactions between icotinib/apatinib and oxycodone in rats and to unveil the underlying mechanism. An ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated to determine oxycodone and its demethylated metabolite simultaneously. , Sprague-Dawley (SD) male rats were administered oxycodone with or without icotinib or apatinib.
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Blue Ridge Institute for Medical Research, 221 Haywood Knolls Drive, Hendersonville, NC 28791-8717, United States. Electronic address:
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November 2023
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
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View Article and Find Full Text PDFFirst-line therapeutic strategy for patients with advanced non-small cell lung cancer with Leu858Arg epidermal growth factor receptor mutations: a Bayesian network meta-analysis.
Ther Adv Chronic Dis
October 2022
State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
Aim: The objective of this network meta-analysis was to determine the most useful first-line therapeutic strategy for patients with advanced (IIIB/IV or relapsed) non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) Leu858Arg or EGFR 19del mutations.
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Department of Clinical Oncology, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
(1) Background: Randomized controlled trials (RCTs) have explored various primary treatments for individuals diagnosed as having later-stage epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer. Nevertheless, the extent to which such treatments are efficacious, particularly with regard to overall survival (OS) rates of patients from Asia with exon 19 deletion (19del), has yet to be clarified. (2) Methods: A systematic review and frequentist network meta-analysis were conducted by obtaining pertinent studies from PubMed/MEDLINE Ovid, Embase, Cochrane Library, and trial registries, as well as various other sources.
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