Therapeutic drug monitoring of immunosuppressive drugs in hepatology and gastroenterology

Udomkarnjananun, Suwasin; Francke, Marith I.; Winter, Brenda C M de; Mulder, Midas B.; Baan, Carla C.; Metselaar, Herold J.; Hoed, Caroline M. den; Hesselink, Dennis A.

doi:10.1016/j.bpg.2021.101756

Cited by 24 publications

(19 citation statements)

References 134 publications

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“…Liquid chromatography coupled to tandem mass spectrometry (MS) detection is the currently preferred choice for determining FK506 in clinical laboratories. − Although this technique provides accurate, reproducible results, it requires sizeable investments and skilled personnel. In addition, it involves long analysis times and time-consuming sample preparation procedures, which result in increased costs and make the hyphenated technique unsuitable for a high-throughput screening.…”

Section: Introductionmentioning

confidence: 99%

Biosensing Tacrolimus in Human Whole Blood by Using a Drug Receptor Fused to the Emerald Green Fluorescent Protein

et al. 2022

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Tacrolimus (FK506) is an immunosuppressant drug (ISD) used to prevent organ rejection after transplantation that exhibits a narrow therapeutic window and is subject to wide interand intra-individual pharmacokinetic fluctuations requiring careful monitoring. The immunosuppressive capacity of FK506 arises from the formation of a complex with immunophilin FKBP1A. This paper describes the use of FKBP1A as an alternative to common antibodies for biosensing purposes. Bioassays use recombinant FKBP1A fused to the emerald green fluorescent protein (FKBP1A−EmGFP). Samples containing the immunosuppressant are incubated with the recombinant protein, and free FKBP1A− EmGFP is captured by magnetic beads functionalized with FK506 to generate a fluorescence signal. Recombinant receptor−drug interaction is evaluated by using a quartz crystal microbalance and nuclear magnetic resonance. The limit of detection (3 ng mL −1 ) and dynamic range thus obtained (5−70 ng mL −1 ) fulfill therapeutic requirements. The assay is selective for other ISD usually coadministered with FK506 and allows the drug to be determined in human whole blood samples from organ transplant patients with results comparing favorably with those of an external laboratory.

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Section: Introductionmentioning

confidence: 99%

Biosensing Tacrolimus in Human Whole Blood by Using a Drug Receptor Fused to the Emerald Green Fluorescent Protein

et al. 2022

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“…Therapeutic drug monitoring (TDM) is essential for optimizing the dosage regimen of drugs with large variations in individual pharmacokinetics, narrow therapeutic windows, and adverse side effects. TDM is widely applied to antineoplastic drugs, [1][2][3][4] immunosuppressive agents, [5][6][7][8][9] antiepileptic drugs, [10][11][12] and antibiotics. [13][14][15] Lenvima (lenvatinib), an oral multikinase inhibitor, has been approved for treating unresectable hepatocellular carcinoma (HCC).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of a Capillary Microsampling Device for Analyzing Plasma Lenvatinib Concentration in Patients With Hepatocellular Carcinoma

Saito

Kikuchi

Matsumoto

et al. 2022

Therapeutic Drug Monitoring

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Background:The anticancer drug, Lenvima (lenvatinib), has severe side effects. Therapeutic drug monitoring helps ensure its efficacy and safety. Regular and optimally timed blood sampling is tough, especially when lenvatinib is self-medicated. Microsampling using the easy to handle Microsampling Wing (MSW) may help circumvent this problem. However, current lenvatinib detection methods are not sensitive enough to detect its concentrations in microsamples (,50-250 mL). Thus, the aim of this study was 2-fold (1) develop an analytic method to estimate plasma lenvatinib concentrations in microsamples and (2) verify whether this method works on micro (5.6 mL) blood plasma samples obtained clinically through MSW from patients with unresectable hepatocellular carcinoma (HCC).Methods: A simple, highly sensitive, and specific liquid chromatography-electrospray ionization tandem mass spectrometry method was developed. Using this novel protocol, the trough blood plasma concentration of lenvatinib was measured for both blood sampled conventionally and that using MSW. Thirty-five venous whole blood samples were obtained from 11 patients with HCC. Furthermore, the stability of lenvatinib in MSW samples during storage was evaluated. Results:The mean plasma lenvatinib concentration estimates were not significantly different between the MSW and conventional venous blood samples. CV for interday and intraday assays was low. Up to day 5, the lenvatinib concentration in the MSW samples was 85%-115% of the initial day concentration (when stored at 258C or 48C). The interference of endogenous matrix components in the human plasma was low. Conclusions:These results indicate that the novel mass spectrometry protocol accurately measures lenvatinib in human plasma and is reproducible. Thus, MSW could be a useful microsampling device for lenvatinib therapeutic drug monitoring in patients with HCC when used in combination with this novel liquid chromatographyelectrospray ionization tandem mass spectrometry detection method.

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“…Drugs of interest are chemicals with a narrow therapeutic window, which regularly pose considerable problems in initial and ongoing dosing [7,8]. These drugs are often subject to polymorphic metabolism with considerable inter-and intra-individual variability requiring TDM for personalised dosage [9]. As these drugs are highly sequestered in erythrocytes and leukocytes, and also reversibly bound to plasma proteins, their concentration is routinely measured nowadays in haemolysed whole blood samples, by means of laboratory techniques, such as liquid chromatography-tandem mass spectrometry (LC-MS/MS) and fluorescence or chemiluminescence immunoassays [8,10,11].…”

Section: Introductionmentioning

confidence: 99%

An integrated device for fast and sensitive immunosuppressant detection

et al. 2021

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The present paper describes a compact point of care (POC) optical device for therapeutic drug monitoring (TDM). The core of the device is a disposable plastic chip where an immunoassay for the determination of immunosuppressants takes place. The chip is designed in order to have ten parallel microchannels allowing the simultaneous detection of more than one analyte with replicate measurements. The device is equipped with a microfluidic system, which provides sample mixing with the necessary chemicals and pumping samples, reagents and buffers into the measurement chip, and with integrated thin film amorphous silicon photodiodes for the fluorescence detection. Submicrometric fluorescent magnetic particles are used as support in the immunoassay in order to improve the efficiency of the assay. In particular, the magnetic feature is used to concentrate the antibody onto the sensing layer leading to a much faster implementation of the assay, while the fluorescent feature is used to increase the optical signal leading to a larger optical dynamic change and consequently a better sensitivity and a lower limit of detection. The design and development of the whole integrated optical device are here illustrated. In addition, detection of mycophenolic acid and cyclosporine A in spiked solutions and in microdialysate samples from patient blood with the implemented device are reported. Graphical abstract

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Therapeutic drug monitoring of immunosuppressive drugs in hepatology and gastroenterology

Cited by 24 publications

References 134 publications

Biosensing Tacrolimus in Human Whole Blood by Using a Drug Receptor Fused to the Emerald Green Fluorescent Protein

Biosensing Tacrolimus in Human Whole Blood by Using a Drug Receptor Fused to the Emerald Green Fluorescent Protein

Evaluation of a Capillary Microsampling Device for Analyzing Plasma Lenvatinib Concentration in Patients With Hepatocellular Carcinoma

An integrated device for fast and sensitive immunosuppressant detection

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