Point-of-Care Therapeutic Drug Monitoring for Precision Dosing of Immunosuppressive Drugs

Abstract

Background Immunosuppressive drugs (ISD) are an essential tool in the treatment of transplant rejection and immune-mediated diseases. Therapeutic drug monitoring (TDM) for determination of ISD concentrations in biological samples is an important instrument for dose personalization for improving efficacy while reducing side effects. While currently ISD concentration measurements are performed at specialized, centralized facilities, making the process complex and laborious for the patient, various innovative technical solutions have recently been proposed for bringing TDM to the point-of-care (POC). Content In this review, we evaluate current ISD-TDM and its value, limitations, and proposed implementations. Then, we discuss the potential of POC-TDM in the era of personalized medicine, and provide an updated review on the unmet needs and available technological solutions for the development of POC-TDM devices for ISD monitoring. Finally, we provide concrete suggestions for the generation of a meaningful and more patient-centric process for ISD monitoring. Summary POC-based ISD monitoring may improve clinical care by reducing turnaround time, by enabling more frequent measurements in order to obtain meaningful pharmacokinetic data (i.e., area under the curve) faster reaction in case of problems and by increasing patient convenience and compliance. The analysis of the ISD-TDM field prompts the evolution of POC testing toward the development of fully integrated platforms able to support clinical decision-making. We identify 4 major areas requiring careful combined implementation: patient usability, data meaningfulness, clinicians’ acceptance, and cost-effectiveness.

Clinical Applications of Visual Plasmonic Colorimetric Sensing

“…On the other hand, the auto-aggregation of nanoparticles caused by non-target-mediated factors such as pH, temperature, solvent and molecules charges may lead to false positive/negative results [34]. In spite of these potential limitations, many colorimetric applications have reported ultrasensitive detection levels of biologically relevant targets for molecular diagnostic purposes and drug discovery by merely using the unaided eye [13,[49][50][51].…”

“…Therapeutic drug monitoring often requires timely measuring of specific drugs at different intervals to ensure constant blood concentrations whilst surveilling patient adherence to treatment [50]. In this context, colorimetric assays offer unique opportunities for the remote biosensing of clinical effects and systemic toxicity in order to optimize drug dosage and patient response at the point of care [51]. The detection of antidepressants is of special interest to manage the relationship between pharmaceutical preparation and therapeutic effects in biological fluids.…”

Analytical Platforms at Swiss Universities of Applied Sciences

“…For many years, conventional sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) has been widely used to monitor identity and purity of therapeutic proteins. [32,33] At the Analytical Platform at the Institute of Life Technologies in addition to the traditional SDS-PAGE, also CGE-SDS was implemented for the analysis of proteins, especially mAbs. Advantages of CGE-SDS in comparison to SDS-PAGE include short analysis time, high reproducibility, and much higher resolution.…”

“…Processing of blood samples obtained from a finger prick were performed using a microfluidic cartridge. To verify that the developed demonstrator met the challenging analytical and clinical specifications, [33] results of tested samples were compared to data obtained with LC-MS methods. [36,37] Fig.…”

An integrated device for fast and sensitive immunosuppressant detection

“…On this basis, it is clear that a device capable to measure frequently immunosuppressants close to transplanted patients is a strong plea of physicians in transplantation surgery for the determination of the right dosage of the administered drugs in the first period after transplantation, increasing the number of relevant or evolving clinical parameters to be analysed with POCT devices [15]. Among the typical immunosuppressants, the calcineurin inhibitors cyclosporine A [16] and tacrolimus (FK 506) [17,18] are of particular interest, as well as mycophenolic acid [19,20], which inhibits an enzyme needed for the growth of T-and B-cells.…”