Feasibility of extrapolating randomly taken plasma samples to trough levels for therapeutic drug monitoring purposes of small molecule kinase inhibitors

Ruben A.G. van Eerden*, Esther Oomen De Hoop, Aad Noordam, Ron H.J. Mathijssen, Stijn L.W. Koolen

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

9 Citations (Scopus)
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Abstract

Small molecule kinase inhibitors (SMKIs) are widely used in oncology. Therapeutic drug monitoring (TDM) for SMKIs could reduce underexposure or overexposure. However, logistical issues such as timing of blood withdrawals hamper its implementation into clinical practice. Extrapolating a random concentration to a trough concentration using the elimination half-life could be a simple and easy way to overcome this problem. In our study plasma concentrations observed during 24 h blood sampling were used for extrapolation to trough levels. The objective was to demonstrate that extrapolation of randomly taken blood samples will lead to equivalent estimated trough samples compared to measured Cmin values. In total 2241 blood samples were analyzed. The estimated Ctrough levels of afatinib and sunitinib fulfilled the equivalence criteria if the samples were drawn after Tmax . The calculated Ctrough levels of erlotinib, imatinib and sorafenib met the equivalence criteria if they were taken, respectively, 12 h, 3 h and 10 h after drug intake. For regorafenib extrapolation was not feasible. In conclusion, extrapolation of randomly taken drug concentrations to a trough concentration using the mean elimination half-life is feasible for multiple SMKIs. Therefore, this simple method could positively contribute to the implementation of TDM in oncology.

Original languageEnglish
Article number119
Pages (from-to)1-10
Number of pages10
JournalPharmaceuticals
Volume14
Issue number2
DOIs
Publication statusPublished - 4 Feb 2021

Bibliographical note

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© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

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  • EMC OR-01

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