MDR1 gene C3435T polymorphism in chronic hepatitis C patients

Nahad, Mehdi Parsa; Makvandi, Manoochehr; Teimoori, Ali; Jalilian, Shahram; Kayedani, Gholam Abbas; Mahmoodi, Sara

doi:10.1016/j.micpath.2017.11.017

Cited by 1 publication

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“…18 Genetic polymorphisms in CYP3A and P-glycoprotein (MDR1) affect the metabolism and absorption, respectively, of lenvatinib. 19,20 Moreover, HCC patients often have advanced cirrhosis due to hepatitis virus infection or excessive alcohol consumption. Advanced cirrhosis may cause individual differences in protein synthesis ability and CYP3A expression, depending on the degree of cirrhosis progression.…”

Section: Introductionmentioning

confidence: 99%

A Broad Range High-Throughput Assay for Lenvatinib Using Ultra-High Performance Liquid Chromatography Coupled to Tandem Mass Spectrometry With Clinical Application in Patients With Hepatocellular Carcinoma

Sueshige

Shiraiwa

Honda

et al. 2021

Therapeutic Drug Monitoring

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Background: Lenvatinib is increasingly being selected as the firstline treatment for unresectable hepatocellular carcinoma (HCC) based on the results of the REFLECT trial. However, early discontinuation of lenvatinib because of adverse effects is a frequent occurrence. Hence, lenvatinib is a difficult drug for use in the clinical setting. One of the causes is that the dose of lenvatinib is mainly determined by body weight alone, despite high interindividual variability. To overcome this problem, a dosing regimen of lenvatinib based on a population pharmacokinetic (PPK) model for HCC patients is proposed. The aim of this study was to develop a high-throughput quantification method for lenvatinib using ultrahigh performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS) that can be applied to a PPK analysis of HCC patients in the future.Methods: After a simple solid-phase extraction step using a 96well plate, lenvatinib was analyzed by UHPLC-MS/MS in a positive electrospray ionization mode. Results:The novel method fulfilled the requirements of the US Food and Drug Administration guidance on bioanalytical method validation. The calibration curve was linear over the 0.2-1000 ng/ mL concentration range. The average recovery rate was 98.63 6 4.55% (mean 6 SD). The precision was below 6.05%, and the accuracy was within 12.96% for all quality control levels. The matrix effect varied between 103.33% and 134.61%. This assay was successfully applied to the measurement of plasma concentrations in 6 HCC patients receiving lenvatinib.Conclusions: A novel high-throughput UHPLC-MS/MS assay for quantification of lenvatinib in human plasma was successfully developed. This method can be applied to PPK analysis for patients receiving lenvatinib in the clinical setting.

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Section: Introductionmentioning

confidence: 99%