Finger-Prick Blood Sampling for Therapeutic Drug Monitoring

Abstract Background & Aims Because of COVID-19 public health restrictions, telemedicine has replaced conventional outpatient follow up for most patients with chronic immune-mediated inflammatory disorders treated with biologic drugs. Innovative solutions to facilitate remote therapeutic drug monitoring are therefore required. Low-volume intracapillary blood sampling can be undertaken by patients at home and samples returned by post to central laboratories. We sought to report the effect of the COVID-19 pandemic on requests for therapeutic drug monitoring and the equivalence, acceptability and effectiveness of low volume Patient-led Remote IntraCapillary pharmacoKinetic Sampling (fingerPRICKS) compared to conventional venepuncture. Methods We undertook a cross-sectional blood sampling methods comparison study and compared sample types using linear regression models. Drug and antidrug antibody levels were measured using standard ELISAs. Acceptability was assessed using a purpose-designed questionnaire. Results Therapeutic drug monitoring requests for adalimumab (96.5 [70.5 - 106] per week to 52 [33.5 - 57.0], p < 0.001) but not infliximab (184.5 [161.2 - 214.2] to 161 [135 – 197.5], p = 0.34) reduced during the first UK stay-at-home lockdown compared with the preceding six months. Fingerprick sampling was equivalent to conventional venepuncture for adalimumab, infliximab, vedolizumab, and ustekinumab drug, and anti-adalimumab and -infliximab antibody levels. The median (IQR) volume of serum obtained using intracapillary sampling was 195µL (130-210). More than 87% (90/103) patients agreed that intracapillary testing was easy and 69% (71/103) preferred it to conventional venepuncture. In routine care, 75.3% (58/77) patients returned two blood samples within 14 days to permit remote assessment of biologic therapeutic drug monitoring. Conclusions Therapeutic drug monitoring can be undertaken using patient-led remote intracapillary blood sampling and has the potential to be a key adjunct to telemedicine in patients with immune-mediated inflammatory diseases.

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Saliva Versus Blood Sampling for Therapeutic Drug Monitoring in Children

Therapeutic Drug Monitoring ◽

10.1097/00007691-199410000-00001 ◽

1994 ◽

Vol 16 (5) ◽

pp. 437-443 ◽

Cited By ~ 43

Author(s):

Rafael Gorodischer ◽

Pascale Burtin ◽

Paul Hwang ◽

Mitchell Levine ◽

Gideon Koren

Keyword(s):

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Blood Sampling ◽

Therapeutic Drug

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Impact of Pharmacist Scheduling of Blood-Sampling Times for Therapeutic Drug Monitoring

American Journal of Health-System Pharmacy ◽

10.1093/ajhp/45.2.380 ◽

1988 ◽

Vol 45 (2) ◽

pp. 380-382 ◽

Cited By ~ 1

Author(s):

Peter J. Ambrose ◽

Michael Nitake ◽

Carl W. Kildoo

Keyword(s):

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Blood Sampling ◽

Therapeutic Drug ◽

Sampling Times

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Dried Blood Spot Analysis Suitable for Therapeutic Drug Monitoring of Voriconazole, Fluconazole, and Posaconazole

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00707-13 ◽

2013 ◽

Vol 57 (10) ◽

pp. 4999-5004 ◽

Cited By ~ 36

Author(s):

Kim C. M. van der Elst ◽

Lambert F. R. Span ◽

Kai van Hateren ◽

Karin M. Vermeulen ◽

Tjip S. van der Werf ◽

...

Keyword(s):

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Sampling Method ◽

Fungal Infections ◽

Venous Blood ◽

Blood Sampling ◽

Dried Blood Spot ◽

Therapeutic Drug ◽

Venous Blood Sampling ◽

Blood Spot

ABSTRACTInvasive aspergillosis and candidemia are important causes of morbidity and mortality in immunocompromised and critically ill patients. The triazoles voriconazole, fluconazole, and posaconazole are widely used for the treatment and prophylaxis of these fungal infections. Due to the variability of the pharmacokinetics of the triazoles among and within individual patients, therapeutic drug monitoring is important for optimizing the efficacy and safety of antifungal treatment. A dried blood spot (DBS) analysis was developed and was clinically validated for voriconazole, fluconazole, and posaconazole in 28 patients. Furthermore, a questionnaire was administered to evaluate the patients' opinions of the sampling method. The DBS analytical method showed linearity over the concentration range measured for all triazoles. Results for accuracy and precision were within accepted ranges; samples were stable at room temperature for at least 12 days; and different hematocrit values and blood spot volumes had no significant influence. The ratio of the drug concentration in DBS samples to that in plasma was 1.0 for voriconazole and fluconazole and 0.9 for posaconazole. Sixty percent of the patients preferred DBS analysis as a sampling method; 15% preferred venous blood sampling; and 25% had no preferred method. There was significantly less perception of pain with the DBS sampling method (P= 0.021). In conclusion, DBS analysis is a reliable alternative to venous blood sampling and can be used for therapeutic drug monitoring of voriconazole, fluconazole, and posaconazole. Patients were satisfied with DBS sampling and had less pain than with venous sampling. Most patients preferred DBS sampling to venous blood sampling.

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Developing a Nationwide Infrastructure for Therapeutic Drug Monitoring of Targeted Oral Anticancer Drugs: The ON-TARGET Study Protocol

Cancers ◽

10.3390/cancers13246281 ◽

2021 ◽

Vol 13 (24) ◽

pp. 6281

Author(s):

Anna Mc Laughlin ◽

Eduard Schmulenson ◽

Olga Teplytska ◽

Sebastian Zimmermann ◽

Patrick Opitz ◽

...

Keyword(s):

Therapeutic Drug Monitoring ◽

Anticancer Drugs ◽

Drug Monitoring ◽

Drug Exposure ◽

Plasma Concentrations ◽

Blood Sampling ◽

Therapeutic Drug ◽

Study Phase ◽

Blood Samples ◽

Drug Concentrations

Exposure-efficacy and/or exposure-toxicity relationships have been identified for up to 80% of oral anticancer drugs (OADs). Usually, OADs are administered at fixed doses despite their high interindividual pharmacokinetic variability resulting in large differences in drug exposure. Consequently, a substantial proportion of patients receive a suboptimal dose. Therapeutic Drug Monitoring (TDM), i.e., dosing based on measured drug concentrations, may be used to improve treatment outcomes. The prospective, multicenter, non-interventional ON-TARGET study (DRKS00025325) aims to investigate the potential of routine TDM to reduce adverse drug reactions in renal cell carcinoma patients receiving axitinib or cabozantinib. Furthermore, the feasibility of using volumetric absorptive microsampling (VAMS), a minimally invasive and easy to handle blood sampling technique, for sample collection is examined. During routine visits, blood samples are collected and sent to bioanalytical laboratories. Venous and VAMS blood samples are collected in the first study phase to facilitate home-based capillary blood sampling in the second study phase. Within one week, the drug plasma concentrations are measured, interpreted, and reported back to the physician. Patients report their drug intake and toxicity using PRO-CTCAE-based questionnaires in dedicated diaries. Ultimately, the ON-TARGET study aims to develop a nationwide infrastructure for TDM for oral anticancer drugs.

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788. Therapeutic Drug Monitoring for Pyrazinamide During Tuberculosis Treatment: What Is the Diagnostic Accuracy?

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy210.795 ◽

2018 ◽

Vol 5 (suppl_1) ◽

pp. S282-S283

Author(s):

Ginger Anderson ◽

Christopher Vinnard

Keyword(s):

High Risk ◽

Therapeutic Drug Monitoring ◽

Diagnostic Accuracy ◽

Roc Curve ◽

Drug Monitoring ◽

Sparse Sampling ◽

Blood Sampling ◽

Successful Outcome ◽

Therapeutic Drug ◽

Blood Levels

Abstract Background Pyrazinamide (PZA) is a key drug for both drug-sensitive and drug-resistant tuberculosis (TB). Patients co-infected with TB and human immunodeficiency virus (HIV) are more likely to have low blood levels of PZA, associated with inferior outcomes. Therapeutic drug monitoring (TDM) with sparse blood sampling is recommended for high-risk groups, including HIV/TB patients, but the accuracy is uncertain. We performed a pharmacokinetic (PK) simulation study to estimate the diagnostic accuracy of TDM for PZA among HIV/TB patients. Methods We recently performed a population PK study among HIV/TB patients in Botswana, identifying a 1-compartment model with first-order elimination. In the current work, we performed an intensive PK simulation (n = 10,000 patients) to determine the accuracy of sparse blood sampling in identifying HIV/TB patients with low PZA blood levels, as defined by the AUC in a dosing interval (AUC0-24) predictive of successful outcome (363 mg*hr/L). PZA dosing followed WHO guidelines with weight-based dosing bands. In secondary analysis, we examined the peak concentration (Cmax) target predictive of 2-month sputum conversion (58 mg/L). To determine the accuracy of sparse sampling (2- and 6-hours), we performed receiver-operating-characteristic (ROC) analysis, with bootstrapping (n = 1,000) for 95% confidence intervals (CI), and defined accuracy as the area under the ROC curve. Results In this simulation PK study of PZA among HIV/TB patients, the PZA AUC0-24 fell below the target in 29% of patients, while in 71% of patients the PZA Cmax was below the target. For the AUC0-24 target, the area under the ROC curve was 0.69 (95% CI 0.68–0.70) for a single 2-hour sample, increasing to 0.75 (95% CI 0.74–0.76) for 2- and 6-hour samples. For the Cmax target, diagnostic accuracy was similar for a 2-hour sample (0.87, 95% CI 0.86–0.87) and 2- and 6-hour samples (0.88, 95% CI 0.88–0.89). Conclusion We observed modest diagnostic accuracy of TDM for identifying in silico HIV/TB patients with low PZA AUC0-24, and higher accuracy for low Cmax. By identifying diagnostic performance characteristics of sparse sampling strategies, including optimal cut-offs, the ROC framework can support wider implementation of TDM in high-risk TB populations. Disclosures All authors: No reported disclosures.

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Cefepime therapeutic drug monitoring: Evaluation of agreement between peripheral and central venous blood sampling

Clinica Chimica Acta ◽

10.1016/j.cca.2020.08.015 ◽

2020 ◽

Vol 510 ◽

pp. 450-454

Author(s):

Matthias Gijsen ◽

Johan Maertens ◽

Katrien Lagrou ◽

Willy E. Peetermans ◽

David Fage ◽

...

Keyword(s):

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Venous Blood ◽

Blood Sampling ◽

Therapeutic Drug ◽

Central Venous ◽

Central Venous Blood ◽

Venous Blood Sampling

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Monographs on drugs which are frequently analyzed in therapeutic drug monitoring/Arzneimittel-Monographien für Medikamente, die regelmäßig im Rahmen des Therapeutic Drug Monitorings analysiert werden

LaboratoriumsMedizin ◽

10.1515/labmed-2011-0013 ◽

2012 ◽

Vol 36 (2) ◽

Keyword(s):

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Clinical Chemistry ◽

Parent Drug ◽

Life Time ◽

Antiretroviral Drugs ◽

Blood Sampling ◽

Therapeutic Drug ◽

Drug Concentrations ◽

The Stability

AbstractIn addition to the monographs which have been published in the past 7 years by the working group “Drug Monitoring” of the Swiss Society of Clinical Chemistry (SSCC) [1–6], new monographs have been written. The data presented in these monographs provide an overview of the information which is important for the request and interpretation of the results. Therefore, laboratory health professionals and the receivers of the reports are the targeted readers. In this series, antiretroviral drugs are presented for which drug concentrations are regularly determined (protease inhibitors, non-nucleoside reverse transcriptase inhibitors). To date, no clear evidence has been established that therapeutic drug monitoring of these drugs increases the success of the antiretroviral therapy. Nevertheless, many cases have demonstrated that the therapy can be guided with much more confidence and with good success if the drug concentrations are determined, especially if the patient has a combination therapy with many pharmacokinetically interfering compounds. First, information is given about pharmacology and pharmacokinetics of these drugs, such as protein binding, metabolic pathways with specific enzymes involved, elimination half-life time, elimination route(s) of the parent drug, as well as therapeutic and toxic concentrations. Moreover, indications for therapeutic drug monitoring are listed with important preanalytical information (time point of blood sampling and time to steady state since beginning or after change of posology). Furthermore, the stability of the drug and its metabolite(s) after blood sampling are described. For readers with a specific interest, references to important publications are given. The number of monographs will be further enlarged. The updated files are presented on the homepage of the SSCC (www.sscc.ch). We hope that these monographs are helpful for the better handling of therapeutic drug monitoring and we are looking forward to receiving comments from the readers.

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P384 Therapeutic drug monitoring: performance of the first lateral flow-based Point of Care test for the quantification of infliximab in a finger prick

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab076.508 ◽

2021 ◽

Vol 15 (Supplement_1) ◽

pp. S396-S397

Author(s):

A Ametzazurra ◽

J Pascual ◽

L Del Rio ◽

A Maguregui ◽

D Nagore ◽

...

Keyword(s):

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Whole Blood ◽

Limit Of Detection ◽

Point Of Care ◽

Package Insert ◽

Lateral Flow ◽

Therapeutic Drug ◽

Limit Of Quantification ◽

Finger Prick

Abstract Background Promonitor Quick IFX is a lateral flow test (LFT) for the quantification of infliximab (IFX) in human whole blood (finger prick or venous) or serum in 20 minutes. This LFT is based on a sandwich immunoassay to quantify either the reference IFX or biosimilars. This abstract describes the studies performed to establish the analytical specifications of the product. Methods Clinical and Laboratory Standards Institute (CLSI) guidelines were followed for the evaluation of the analytical specifications of the LFT in whole blood and serum matrices: Linearity (EP-06-A), Detection capability (EP17-A2), Interfering substances (EP07, 3rd Edition), Intermediate precision (EP05-A3) and Bias evaluation study for Biosimilars (EP10-A3). Results were obtained in combination with the automated portable reader PQreader. A Datamatrix provided with each Promonitor Quick IFX kit contains the calibration information required for the PQreader to measure the Control and Test lines and report the IFX concentration. Results The linear assay range was determined to be 1-58 µg/mL in whole-blood and 0.6-67 µg/mL in serum according to the processes indicated in the Package Insert. The Limit of Blank is 0.8 μg/mL, the Limit of Detection and Lower Limit of Quantification (LLoQ) are 1.1 μg/mL, and the Upper Limit of Quantification (ULoQ) is 15.4 μg/mL. There was no effect on assay performance when each of the following substances were added to samples with 0, 3, and 7 μg/mL of IFX: Haemoglobin (>1000 mg/dL), Bilirubin (>40 mg/dL), Triglycerides (>1500 mg/dL), HAMA (160 AU/mL), Rheumatoid factor (200 IU/mL), EDTA (5.4 mg/mL), Heparin (51 U/mL), Citrate (11.4%), Vedolizumab (60 μg/mL) and Adalimumab (20.25 μg/mL). Repeatability and within-device precision results obtained for the positive samples are shown in the table below. The negative samples showed a negative result in all the measurements. A bias study showed that Promonitor Quick IFX can quantify CT-P13, SB2 and GP1111 biosimilars throughout the measurement range with a maximum bias of 14%. Conclusion Promonitor Quick IFX is the first LFT available for true Point of Care testing of patients treated with IFX with just a finger prick sample. It provides quick turnaround time to facilitate therapeutic drug monitoring and aid immediate decision making in the doctor office or hospitals with an excellent analytical performance.

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P181 Patient-led remote intracapillary pharmacokinetic sampling (fingerPRICKS) for therapeutic drug monitoring in patients with Inflammatory Bowel Disease

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab076.308 ◽

2021 ◽

Vol 15 (Supplement_1) ◽

pp. S252-S252

Author(s):

D Chee ◽

R Nice ◽

B Hamilton ◽

E Jones ◽

S Hawkins ◽

...

Keyword(s):

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Inflammatory Diseases ◽

Blood Sampling ◽

Therapeutic Drug ◽

Biologic Drugs ◽

Immune Mediated ◽

Low Volume ◽

Antibody Levels ◽

At Home

Abstract Background Because of COVID-19 public health restrictions, telemedicine has replaced conventional outpatient follow up for most patients with chronic immune-mediated inflammatory disorders treated with biologic drugs. Innovative solutions to facilitate remote therapeutic drug monitoring are therefore required. Low-volume intracapillary blood sampling can be undertaken by patients at home and samples returned by post to central laboratories. Methods We sought to report the effect of the COVID-19 pandemic on requests for therapeutic drug monitoring and the equivalence, acceptability and effectiveness of low-volume intracapillary fingerprick sampling compared to conventional venepuncture. Drug and antidrug antibody levels were measured using standard ELISAs. Results Therapeutic drug monitoring requests for adalimumab (96.5 [70.5 - 106] per week to 52 [33.5 - 57.0], p < 0.001) but not infliximab (184.5 [161.2 - 214.2] to 161 [135 - 197.5], p = 0.34) reduced during the first UK stay-at-home lockdown compared with the preceding six months. Fingerprick sampling was equivalent to conventional venepuncture for adalimumab (Figure 1), infliximab, vedolizumab, and ustekinumab drug and anti-adalimumab and -infliximab antibody levels. The median (IQR) volume of serum obtained using intracapillary sampling was 195µL (130–210). More than 87% (90/103) patients agreed that intracapillary testing was easy and 69% (71/103) preferred it to conventional venepuncture (Figure 2). In routine care, 75.3% (58/77) patients returned two blood samples within 14 days to permit remote assessment of biologic therapeutic drug monitoring. Conclusion Therapeutic drug monitoring can be undertaken using patient-led remote intracapillary blood sampling and has the potential to be a key adjunct to telemedicine in patients with immune-mediated inflammatory diseases.

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