Plasma vs whole blood for therapeutic drug monitoring of patients receiving FK 506 for immunosuppression

1994 ◽  
Vol 40 (12) ◽  
pp. 2247-2253 ◽  
Author(s):  
M Winkler ◽  
B Ringe ◽  
J Baumann ◽  
M Loss ◽  
K Wonigeit ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Enzyme Immunoassay ◽  
Drug Monitoring ◽  
Whole Blood ◽  
Plasma Concentrations ◽  
Therapeutic Monitoring ◽  
Therapeutic Drug ◽  
Fk 506 ◽  
Blood Samples ◽  
The Matrix

Abstract By retrospective analysis of 13,000 blood samples obtained from 248 patients receiving FK 506 therapy, we compared the suitability of plasma with that of whole blood as the matrix for therapeutic drug monitoring of FK 506. The plasma concentrations did not correlate with the concentrations in whole blood (r = 0.56). In contrast to plasma samples (analyzed by enzyme immunoassay), FK 506 was detectable in all whole-blood samples (analyzed by enzyme immunoassay/microparticle enzyme immunoassay). The inter- and intraindividual variations of FK 506 measurements were greater in plasma than in whole blood. Moreover, plasma concentrations correlated only poorly with clinical events. There was a tendency to greater plasma concentrations being measured during episodes of toxicity, but no clear difference was evident between stable course and rejection. In whole-blood specimens, a correlation between reduced or increased FK 506 concentrations and rejection or toxicity, respectively, was observed. The discriminatory power of whole-blood values was greater for the differentiation between toxicity and stable course than between rejection and stable course. We therefore recommend whole blood rather than plasma as the matrix for therapeutic monitoring of FK 506 concentrations.

scholarly journals Real-life isoniazid and rifampicin plasma concentrations in children: a tool for therapeutic drug monitoring of tuberculosis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chiara Tersigni ◽  
Giulia Boiardi ◽  
Lorenzo Tofani ◽  
Elisabetta Venturini ◽  
Carlotta Montagnani ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Venous Blood ◽  
Plasma Concentrations ◽  
Age Groups ◽  
Real Life ◽  
Therapeutic Drug ◽  
Blood Samples ◽  
Drug Concentrations

Abstract Background Low plasma levels of first-line antitubercular drugs can be counted among the main causes of poor response to antitubercular therapy, and therapeutic drug monitoring has been proposed as a method to promote tailored treatments for both child and adult patients. The main aim of the study was to evaluate serum concentrations of isoniazid (INH) and rifampicin (RIF) and to investigate reasons for sub-therapeutic plasma concentrations in order to fix dosages. Methods Children with TB were prospectively enrolled from January to August 2019. Two venous blood samples were collected (the first at least 15 days after the beginning of antitubercular treatment, and the second between 1 and 8 weeks later). Plasma concentrations were determined by a validated high-performance liquid chromatography method. Results In all, 45 children were included. Seventy blood samples for INH plasma concentration were collected between 120 and 240 min after drug intake. Adjusting for dose (mg/kg/day) and time of INH administration, when considering three different age groups (≤ 2 years, 2–12 years, > 12 years), a statistically significant lower INH plasma concentration was observed in younger children compared to the older age groups in the multivariate analysis (p < 0.001 and p < 0.001). A total of 68 blood samples were evaluated for RIF concentrations. Both for INH and RIF a statistically significant lower plasma concentration was also observed in adolescents (p < 0.001). Fifteen children (15/45, 33%) presented drug concentrations under the referral therapeutic range. Conclusions Based on our findings, monitoring patients’ drug plasma concentrations in children under 2 years of age and in adolescents can make treatment more patient-tailored.

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

Cancers ◽  
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.

Immunosuppressant therapeutic drug monitoring by LC-MS/MS: Workflow optimization through automated processing of whole blood samples

2013 ◽  
Vol 46 (16-17) ◽  
pp. 1723-1727 ◽  
Author(s):  
Mariela Marinova ◽  
Carlo Artusi ◽  
Laura Brugnolo ◽  
Giorgia Antonelli ◽  
Martina Zaninotto ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Whole Blood ◽  
Therapeutic Drug ◽  
Blood Samples ◽  
Workflow Optimization ◽  
Automated Processing ◽  
Whole Blood Samples

scholarly journals Impact on Antibiotic Resistance, Therapeutic Success, and Control of Side Effects in Therapeutic Drug Monitoring (TDM) of Daptomycin: A Scoping Review

Antibiotics ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 263
Author(s):  
Carolina Osorio ◽  
Laura Garzón ◽  
Diego Jaimes ◽  
Edwin Silva ◽  
Rosa-Helena Bustos
Keyword(s):  
Side Effects ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Bacterial Resistance ◽  
Plasma Concentrations ◽  
Resistant Bacteria ◽  
Therapeutic Drug ◽  
Therapeutic Success ◽  
Favorable Clinical Outcome ◽  
And Control

Antimicrobial resistance (AR) is a problem that threatens the search for adequate safe and effective antibiotic therapy against multi-resistant bacteria like methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococci (VRE) and Clostridium difficile, among others. Daptomycin is the treatment of choice for some infections caused by Gram-positive bacteria, indicated most of the time in patients with special clinical conditions where its high pharmacokinetic variability (PK) does not allow adequate plasma concentrations to be reached. The objective of this review is to describe the data available about the type of therapeutic drug monitoring (TDM) method used and described so far in hospitalized patients with daptomycin and to describe its impact on therapeutic success, suppression of bacterial resistance, and control of side effects. The need to create worldwide strategies for the appropriate use of antibiotics is clear, and one of these is the performance of therapeutic drug monitoring (TDM). TDM helps to achieve a dose adjustment and obtain a favorable clinical outcome for patients by measuring plasma concentrations of an administered drug, making a rational interpretation guided by a predefined concentration range, and, thus, adjusting dosages individually.

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

2021 ◽  
Vol 14 (2) ◽  
pp. 119
Author(s):  
Ruben A. G. van Eerden ◽  
Esther Oomen-de Hoop ◽  
Aad Noordam ◽  
Ron H. J. Mathijssen ◽  
Stijn L. W. Koolen
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Small Molecule ◽  
Trough Concentration ◽  
Drug Monitoring ◽  
Half Life ◽  
Kinase Inhibitors ◽  
Therapeutic Drug ◽  
Blood Samples ◽  
Elimination Half ◽  
Trough Levels

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.

scholarly journals Software for Dosage Individualization of Voriconazole for Immunocompromised Patients

2013 ◽  
Vol 57 (4) ◽  
pp. 1888-1894 ◽  
Author(s):  
William W. Hope ◽  
Michael VanGuilder ◽  
J. Peter Donnelly ◽  
Nicole M. A. Blijlevens ◽  
Roger J. M. Brüggemann ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Fungal Infections ◽  
Plasma Concentrations ◽  
Therapeutic Drug ◽  
Cell Transplant ◽  
Multiple Model ◽  
Pharmacokinetic Variability ◽  
Hematopoietic Stem ◽  
Wide Range

ABSTRACTThe efficacy of voriconazole is potentially compromised by considerable pharmacokinetic variability. There are increasing insights into voriconazole concentrations that are safe and effective for treatment of invasive fungal infections. Therapeutic drug monitoring is increasingly advocated. Software to aid in the individualization of dosing would be an extremely useful clinical tool. We developed software to enable the individualization of voriconazole dosing to attain predefined serum concentration targets. The process of individualized voriconazole therapy was based on concepts of Bayesian stochastic adaptive control. Multiple-model dosage design with feedback control was used to calculate dosages that achieved desired concentration targets with maximum precision. The performance of the software program was assessed using the data from 10 recipients of an allogeneic hematopoietic stem cell transplant (HSCT) receiving intravenous (i.v.) voriconazole. The program was able to model the plasma concentrations with a high level of precision, despite the wide range of concentration trajectories and interindividual pharmacokinetic variability. The voriconazole concentrations predicted after the last dosages were largely concordant with those actually measured. Simulations provided an illustration of the way in which the software can be used to adjust dosages of patients falling outside desired concentration targets. This software appears to be an extremely useful tool to further optimize voriconazole therapy and aid in therapeutic drug monitoring. Further prospective studies are now required to define the utility of the controller in daily clinical practice.

Therapeutic Drug Monitoring: Psychotropic Drugs

1989 ◽  
Vol 2 (6) ◽  
pp. 403-415 ◽  
Author(s):  
Randall D. Seifert
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Antipsychotic Drugs ◽  
Practical Knowledge ◽  
Therapeutic Monitoring ◽  
Therapeutic Drug ◽  
Clinical Use ◽  
Careful Patient ◽  
Recovery Expectations ◽  
Positive Results

The therapeutic monitoring of patients who take antipsychotic drugs can be both challenging and rewarding. Antipsychotics have been in clinical use for over 30 years; yet, their complex pharmacology is not fully understood and parallels our infant knowledge of human brain chemistry. The art of successful therapeutic drug monitoring depends on the clinician's knowledge of basic pharmacology, an understanding of psychiatric disorders, and a sensitivity for careful patient observation. In addition, a thorough history, well thought out goals, and reasonable recovery expectations are essential. Antipsychotic drugs are never curative and should be used judiciously for indications where positive results outweigh the risks of adverse effects. This article will provide the reader with sound, practical knowledge of how to monitor these drugs in any clinical setting. © 1989 by W.B. Saunders Company.

scholarly journals Quantification of 15 Antibiotics Widely Used in the Critical Care Unit with a LC-MS/MS System: An Easy Method to Perform a Daily Therapeutic Drug Monitoring

2021 ◽  
Vol 14 (12) ◽  
pp. 1214
Author(s):  
Catherine Feliu ◽  
Celine Konecki ◽  
Tristan Candau ◽  
Damien Vautier ◽  
Cyril Haudecoeur ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Plasma Concentrations ◽  
Ultra Performance Liquid Chromatography ◽  
Therapeutic Drug ◽  
Beta Lactams ◽  
Quadrupole Mass ◽  
Triple Quadrupole Mass Spectrometer ◽  
Easy Method ◽  
Routine Therapeutic Drug Monitoring

Potential under- or overdose of antibiotics may occur in intensive care units due to high variability in plasma concentrations. The risk is either treatment failure or toxicity. Thus, therapeutic drug monitoring of antibiotics may guide dosing adjustment, maximising antibacterial efficacy and minimising toxicity. The aim of this study was to develop and validate a method for the analysis of 15 antibiotics including beta-lactams, linezolid, fluoroquinolones, daptomycin, and clindamycin to have a complete panel in the management of infections. We proposed to develop a fast, sensitive, and quantitative method for the analysis of 15 antibiotics using ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometer (UPLC-MS/MS) technology. this method required only 100 µL of plasma and consisted of a rapid liquid–liquid deproteinisation using methanol. Calibration curves ranged from 0.078 to 500 mg/L depending on the molecules, and were defined according to a therapeutic range. Inter- and intra-assay precisions values were less than 15%. This work described the development and the full validation of a precise, sensitive and accurate assay using UPLC-MS/MS technology. After validation, this new assay was successfully applied to routine therapeutic drug monitoring.

scholarly journals Is It Time for Systematic Voriconazole Pharmacogenomic Investigation for Central Nervous System Aspergillosis?

2018 ◽  
Vol 62 (9) ◽  
Author(s):  
François Danion ◽  
Vincent Jullien ◽  
Claire Rouzaud ◽  
Manal Abdel Fattah ◽  
Simona Lapusan ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Therapeutic Drug Monitoring ◽  
Invasive Aspergillosis ◽  
Drug Monitoring ◽  
Standard Treatment ◽  
Plasma Concentrations ◽  
Therapeutic Drug ◽  
Life Threatening ◽  
Trough Plasma

ABSTRACT Voriconazole is the standard treatment for invasive aspergillosis but requires therapeutic drug monitoring to optimize therapy. We report two cases of central nervous system aspergillosis treated with voriconazole. Because of low trough plasma concentrations, we identified gain-of-function mutations in CYP2C19 that were partially responsible for the therapeutic failure of voriconazole. We suggest that systematic voriconazole pharmacogenomic investigation of cerebral aspergillosis be performed to avoid effective therapy delay in this life-threatening disease.

SPCCTDM, a Catalogue for Analysis of Therapeutic Drug Monitoring Related Contents

2013 ◽  
pp. 319-328
Author(s):  
Sven Ulrich ◽  
Pierre Baumann ◽  
Andreas Conca ◽  
Hans-Joachim Kuss ◽  
Viktoria Stieffenhofer ◽  
...  
Keyword(s):  
Drug Therapy ◽  
Therapeutic Drug Monitoring ◽  
Text Mining ◽  
Drug Monitoring ◽  
Text Analysis ◽  
Scientific Evidence ◽  
Plasma Concentrations ◽  
Therapeutic Drug ◽  
Drug Reactions ◽  
First Time

Therapeutic drug monitoring (TDM) has consistently been shown to be useful for optimization of drug therapy. For the first time, a method has been developed for the text analysis of TDM in SPCs in that a catalogue SPC-ContentTDM (SPCCTDM) provides a codification of the content of TDM in SPCs. It consists of six structure-related items (dose, adverse drug reactions, drug interactions, overdose, pregnancy/breast feeding, and pharmacokinetics) according to implicit or explicit references to TDM in paragraphs of the SPC, and four theory-guided items according to the information about ranges of plasma concentrations and a recommendation of TDM in the SPC. The catalogue is regarded as valid for the text analysis of SPCs with respect to TDM. It can be used in the comparison of SPCs, in the comparison with medico-scientific evidence and for the estimation of the perception of TDM in SPCs by the reader. Regarding the approach as a model of text mining, it may be extended for evaluation of other aspects reported in SPCs.

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