Feasibility of Extrapolating Randomly Taken Plasma Samples to Trough Levels for Therapeutic Drug Monitoring Purposes of Small Molecule Kinase Inhibitors

• Main Authors: Ruben A. G. van Eerden (Author), Esther Oomen-de Hoop (Author), Aad Noordam (Author), Ron H. J. Mathijssen (Author), Stijn L. W. Koolen (Author)
• Format: Book
• Published: MDPI AG, 2021-02-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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 C_min values. In total 2241 blood samples were analyzed. The estimated C_trough levels of afatinib and sunitinib fulfilled the equivalence criteria if the samples were drawn after T_max. The calculated C_trough 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.

Item Description

10.3390/ph14020119
1424-8247