Therapeutic Drug Monitoring of Venlafaxine and Impact of Age, Gender, BMI, and Diagnosis

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
M. Krivosova ◽  
M. Kertys ◽  
M. Grendar ◽  
I. Ondrejka ◽  
I. Hrtanek ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Active Metabolite ◽  
Common Mental Disorder ◽  
Plasma Concentrations ◽  
Therapeutic Drug ◽  
Active Moiety ◽  
Drug Concentrations ◽  
First Choice ◽  
Significant Difference

AbstractDepression is a common mental disorder affecting more than 264 million people in the world and 5.1% of the Slovak population. Although various antidepressant approaches have been used; still, about 40% of patients do not respond to a first-choice drug administration and one third of patients do not achieve total remission. Therapeutic drug monitoring (TDM) is a method used for quantification and interpreting the drug concentrations in plasma in order to optimize the pharmacotherapy. The aim of this study was to measure the plasma concentrations of venlafaxine, the fourth most prescribed antidepressant in Slovakia, as well as its active metabolite and interpret them with the relevant patients’ characteristics.The study was of retrospective nature and 28 adult patients in total were included. The concentrations of venlafaxine and its active metabolite O-desmethylvenlafaxine (ODV) in plasma were quantified using the validated UHPLC-MS/MS method. The effects of potential influencing factors were evaluated by a multivariate linear regression model.Only 39% of patients reached the venlafaxine active moiety concentrations within the recommended therapeutic range. Plasma concentrations were dependent on age, gender, and duration of the therapy. Venlafaxine metabolism expressed as a metabolite-to-parent concentrations ratio was influenced by a combination of age, gender, and body mass index (BMI). We did not observe any significant difference in plasma concentrations between the patients with a single and recurrent diagnosis of depression. Combining variables made an additive effect on plasma concentrations, for example, active moiety plasma concentrations were higher in older women. In contrast, drug metabolism was higher in older men and men with lower BMI. TDM of venlafaxine is recommended in clinical practice, especially in the elderly when beginning the pharmacotherapy.

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.

Concomitant Use of Cotrimoxazole and Atazanavir in HIV-infected Patients: A Therapeutic Drug Monitoring and Pharmacovigilance Based Dual Approach

2019 ◽  
Vol 14 (3) ◽  
pp. 214-223 ◽  
Author(s):  
Miantezila B. Joe ◽  
Landman Roland ◽  
Chouchana Laurent ◽  
Lê M. Patrick ◽  
Olivier Sawoo ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Odds Ratio ◽  
Opportunistic Infections ◽  
Cohort Analysis ◽  
Plasma Concentrations ◽  
Therapeutic Drug ◽  
Reporting Odds Ratio ◽  
Historical Cohort ◽  
Significant Difference

Background: Cotrimoxazole is the main antibiotic used in primary prophylaxis for opportunistic infections in advanced HIV infection. This drug can inhibit one of the metabolic pathways of atazanavir (ATV), such as the cytochromes P450 (CYP) 2C8/2C9 and could interfere with its safety and efficacy. Objective: We studied the drug-drug interaction (DDI) between cotrimoxazole and ATV by using therapeutic drug monitoring (TDM) and pharmacovigilance (PV) approaches. Methods: We compared a group of patients treated with cotrimoxazole and receiving an ATV-based regimen to controls. This historical cohort analysis used data from Dat’AIDS in HIV-infected patients who had at least two lowest plasma concentrations (C-trough) of ATV during their outpatient follow-up. Likewise, we used the international pharmacovigilance data from VigiBase to evaluate the notifications of hyperbilirubinemia reported with ATV. Results: In the TDM analysis, the two groups of patients (treated with cotrimoxazole and controls) were almost homogeneous concerning the main baseline features. After at least six months of ATVbased regimen, there was no significant difference in the safety threshold of the ATV C-trough [with an adjusted odds ratio (aOR) of 1.4 (95% CI: 0.5 - 4.4)] compared to controls. We observed similar results with the efficacy thresholds of ATV C-trough. Regarding the PV analysis, there was no difference in hyperbilirubinemia occurring with ATV when cotrimoxazole was concomitant, with an adjusted reporting odds ratio (aROR) of 0.9 (95% CI: 0.6 to 1.2). Conclusion: This study showed a relevant concomitant use between Cotrimoxazole and ATV based on TDM and PV approaches.

Abstract 11598: Is Therapeutic Drug Monitoring of Direct Anticoagulants Really Unnecessary?

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Bernadette Baldin ◽  
Marion Warembourg ◽  
Guillaume Bardy ◽  
Loïc Startari ◽  
Fanny Rocher ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Medical Center ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Plasma Concentrations ◽  
Therapeutic Drug ◽  
Drug Concentrations ◽  
Increased Risk ◽  
Direct Anticoagulants

Introduction: no routine monitoring is deemed necessary with direct oral anticoagulants dabigatran (D) and rivaroxaban(R). Yet, their misuse may lead to inefficacy or increased risk of bleeding. Hypothesis: due to the prevalence of elderly patients in our medical center, the pharmacology department was asked to measure R and D plasma concentrations. Therefore we aimed not only to check their prescription adequacy but also to evaluate whether bleeding or thrombosis adverse events were associated with drug concentrations clearly outside of their expected “normal” range. Methods: Patients receiving R or D for either AFib, deep venous thrombosis or its prevention were included and had blood samples drawn for drug measurements, by HPLC-tandem mass spectrometry. Adequacy of the patient prescription was checked by pharmacists according D & R respective SmPCs. A robust and conservative method was applied to evaluate anticoagulant concentrations : D & R concentrations were blindly deemed “normal” when within the [IC] 95 limits (peak and trough, relative to the dose) observed in the respective RE-LY and Rocket-AF pivotal studies, as compared to “out of range” when outside of these limits. Results: 287 consecutive patients from our center had their concentration of R (n=219 : 76%) or D (n = 68 : 24%) measured. The inadequacy of the prescriptions was 31.4% alltogether. Seventy patients presented with bleeding (n = 48, 17%) or thrombosis (n = 22, 8%), that either led to their admission in emergency, or occurred in the hospital wards. Bleedings and thrombosis were significantly associated with out-of-range concentrations (p<0.01). Patients with hemorrhages had higher concentrations (R: 194 VS 83 μg.l -1 and D: 128 VS 80 μg.l -1 ) whereas thrombosis were associated with lower ones (R: 75 VS 106 μg.l -1 D: 29 VS 93 μg.l -1 ). HAS-BLED Score was 2.0 ± 0.9 for bleeding cases as compared to 1.5 ± 0.9 (p<0.01). Conclusions: therapeutic drug monitoring of direct oral anticoagulants might not be superfluous, at least for R & D, especially in patients with a higher score HAS-BLED.

scholarly journals Biosensor-enabled on-site therapeutic drug monitoring of antibiotics

2021 ◽  
Author(s):  
Can Dincer ◽  
Hatice Ceren Ates ◽  
Hasti Mohsenin ◽  
Christin Wenzel ◽  
Regina Glatz ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Point Of Care ◽  
Exhaled Breath Condensate ◽  
Plasma Concentrations ◽  
Therapeutic Drug ◽  
Optimal Dosage ◽  
Large Animal ◽  
Exhaled Breath ◽  
Drug Concentrations

Abstract Antimicrobial resistance is increasing with an alarming rate for which the prime suspect is the “one size-fits-all” dosage strategies of antibiotics. Personalized antibiotherapy framework appears as a viable option to counteract inadequate dosage, as it offers the application of the optimal dosage regimen for each individual. Such individualized scheme, however, needs frequent sampling to tailor the blood antibiotic concentration to respond unique pharmacokinetic/pharmacodynamic (PK/PD) of the patient. Herein, there are two alternative paths for feasible therapeutic drug monitoring (TDM); transforming our understanding to utilize blood based sampling within the scope of point-of-care (POC), or focusing on non-invasive samples. Here, we present a versatile biosensor along with an antibody-free assay that can be utilized in both paths for on-site TDM. The developed platform is evaluated in a large animal study (pigs exposed with overdose, normal dose, and underdose of ß lactams), in which antibiotic concentrations are quantified in matrices including whole blood, plasma, urine, saliva, and exhaled breath condensate (EBC). Herein, the detection and the clearance of drug concentrations in EBC is demonstrated for the first time. Influence of the secretion mechanisms on measured drug concentrations is then quantified by comparing the plasma concentrations with those in EBC, saliva and urine. The potential of the developed platform for blood-based POC application is further illustrated by tracking ß lactam concentrations in untreated blood samples. Finally, multiplexing capabilities are explored successfully for multianalyte/sample analysis. Enabling a rapid, low-cost, sample-independent, and multiplexed on-site TDM, this system could pave the way for the personalized drug therapies and thus, shift the paradigm of “one size-fits-all” strategies.

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 Rapid point-of-care anti-infliximab antibodies detection in clinical practice: comparison with ELISA and potential for improving therapeutic drug monitoring in IBD patients

2021 ◽  
Vol 14 ◽  
pp. 175628482199990
Author(s):  
Sonia Facchin ◽  
Andrea Buda ◽  
Romilda Cardin ◽  
Nada Agbariah ◽  
Fabiana Zingone ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Point Of Care ◽  
Drug Clearance ◽  
Elisa Test ◽  
Enzyme Linked Immunosorbent Assay ◽  
Therapeutic Drug ◽  
Drug Concentrations ◽  
Inflammatory Bowel

Anti-drug antibodies can interfere with the activity of anti-tumor necrosis factor (TNF) agents by increasing drug clearance via direct neutralization. The presence of anti-drug antibodies is clinically relevant when trough drug concentrations are undetectable or sub-therapeutic. However, traditional immunoassay is not easily and rapidly accessible, making the translation of the results into treatment adjustment difficult. The availability of a point-of-care (POC) test for therapeutic drug monitoring (TDM) might represent an important step forward for improving the management of inflammatory bowel disease (IBD) patients in clinical practice. In this pilot study, we compared the results obtained with POC tests with those obtained by enzyme-linked immunosorbent assay (ELISA) in a group of IBD patients treated with Infliximab (IFX). We showed that POC test can reliably detect presence of antibody-to-IFX with 100% of specificity and 76% sensitivity, in strong agreement with the ELISA test ( k-coefficient = 0.84).

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.

Immunosuppressant quantification in intravenous microdialysate – towards novel quasi-continuous therapeutic drug monitoring in transplanted patients

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Susanne Weber ◽  
Sara Tombelli ◽  
Ambra Giannetti ◽  
Cosimo Trono ◽  
Mark O’Connell ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Real Time ◽  
Drug Monitoring ◽  
Time Course ◽  
Drug Dosage ◽  
Immunosuppressive Drug ◽  
Therapeutic Drug ◽  
Continuous Sampling ◽  
Real Time Analysis ◽  
Drug Concentrations

AbstractObjectivesTherapeutic drug monitoring (TDM) plays a crucial role in personalized medicine. It helps clinicians to tailor drug dosage for optimized therapy through understanding the underlying complex pharmacokinetics and pharmacodynamics. Conventional, non-continuous TDM fails to provide real-time information, which is particularly important for the initial phase of immunosuppressant therapy, e.g., with cyclosporine (CsA) and mycophenolic acid (MPA).MethodsWe analyzed the time course over 8 h of total and free of immunosuppressive drug (CsA and MPA) concentrations measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in 16 kidney transplant patients. Besides repeated blood sampling, intravenous microdialysis was used for continuous sampling. Free drug concentrations were determined from ultracentrifuged EDTA-plasma (UC) and compared with the drug concentrations in the respective microdialysate (µD). µDs were additionally analyzed for free CsA using a novel immunosensor chip integrated into a fluorescence detection platform. The potential of microdialysis coupled with an optical immunosensor for the TDM of immunosuppressants was assessed.ResultsUsing LC-MS/MS, the free concentrations of CsA (fCsA) and MPA (fMPA) were detectable and the time courses of total and free CsA comparable. fCsA and fMPA and area-under-the-curves (AUCs) in µDs correlated well with those determined in UCs (r≥0.79 and r≥0.88, respectively). Moreover, fCsA in µDs measured with the immunosensor correlated clearly with those determined by LC-MS/MS (r=0.82).ConclusionsThe new microdialysis-supported immunosensor allows real-time analysis of immunosuppressants and tailor-made dosing according to the AUC concept. It readily lends itself to future applications as minimally invasive and continuous near-patient TDM.

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.

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