Academic Journal

In vitro PK/PD modeling of tyrosine kinase inhibitors in non‐small cell lung cancer cell lines

التفاصيل البيبلوغرافية
العنوان: In vitro PK/PD modeling of tyrosine kinase inhibitors in non‐small cell lung cancer cell lines
المؤلفون: Wanika, Linda, Evans, Neil D., Johnson, M., Tomkinson, H., Chappell, M. J.
بيانات النشر: Wiley Open Access
سنة النشر: 2024
المجموعة: The University of Warwick: WRAP - Warwick Research Archive Portal
الوصف: Tyrosine Kinase inhibitors (TKIs) are routinely prescribed for the treatment of non-small cell lung cancer (NSCLC). As with all medications, patients can experience adverse events due to TKIs. Unfortunately, the relationship between many TKIs and the occurrence of certain adverse events remains unclear. There are limited in-vivo studies which focus on TKIs and their effects on different regulation pathways. Many in-vitro studies, however, that investigate the effects of TKIs observe additional changes such as changes in gene activations or protein expressions. These studies could potentially help to gain greater understanding of the mechanisms for TKI induced adverse events. However, in order to utilise these pathways in a pharmacokinetic / pharmacodynamic (PK/PD) framework, an in-vitro PK/PD model needs to be developed, in order to characterise the effects of TKIs in NSCLC cell lines. Through the use of ordinary differential equations, cell viability data and non-linear mixed effects modelling, an in-vitro TKI PK/PD model was developed with estimated PK and PD parameter values for the TKIs alectinib, crizotinib, erlotinib and gefitinib. The relative standard errors (R.S.E) for the population parameters are all less than 25. The inclusion of random effects enabled the model to predict individual parameter values which provided a closer fit to the observed response. It is hoped that this model can be extended to include in-vitro data of certain pathways that may potentially be linked with adverse events and provide a better understanding to of TKI induced adverse events.
نوع الوثيقة: article in journal/newspaper
وصف الملف: application/pdf
اللغة: unknown
Relation: https://wrap.warwick.ac.uk/182654/7/Clinical%20Translational%20Sci%20-%202024%20-%20Wanika%20-%20In%20vitro%20PK%20PD%20modeling%20of%20tyrosine%20kinase%20inhibitors%20in%20non%E2%80%90small%20cell%20lung.pdf; https://wrap.warwick.ac.uk/182654/1/engineering-180124-wrap--cts_mainarticle_revised_accepted.pdf; Wanika, Linda, Evans, Neil D., Johnson, M., Tomkinson, H. and Chappell, M. J. (2024) In vitro PK/PD modeling of tyrosine kinase inhibitors in non‐small cell lung cancer cell lines. Clinical and Translational Sciences, 17 (3). e13714. doi:10.1111/cts.13714 (In Press)
DOI: 10.1111/cts.13714
الاتاحة: https://wrap.warwick.ac.uk/182654/
https://wrap.warwick.ac.uk/182654/7/Clinical%20Translational%20Sci%20-%202024%20-%20Wanika%20-%20In%20vitro%20PK%20PD%20modeling%20of%20tyrosine%20kinase%20inhibitors%20in%20non%E2%80%90small%20cell%20lung.pdf
https://wrap.warwick.ac.uk/182654/1/engineering-180124-wrap--cts_mainarticle_revised_accepted.pdf
https://doi.org/10.1111/cts.13714
رقم الانضمام: edsbas.181A8680
قاعدة البيانات: BASE
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