Therapeutic drug monitoring assay development to improve efficacy and safety

Daptomycin is a candidate for therapeutic drug monitoring (TDM). The objectives of this work were to implement and compare two pharmacometric tools for daptomycin TDM and precision dosing. A nonparametric population PK model developed from patients with bone and joint infection was implemented into the BestDose software. A published parametric model was imported into Tucuxi. We compared the performance of the two models in a validation dataset based on mean error (ME) and mean absolute percent error (MAPE) of individual predictions, estimated exposure and predicted doses necessary to achieve daptomycin efficacy and safety PK/PD targets. The BestDose model described the data very well in the learning dataset. In the validation dataset (94 patients, 264 concentrations), 21.3% of patients were underexposed (AUC24h < 666 mg.h/L) and 31.9% of patients were overexposed (Cmin > 24.3 mg/L) on the first TDM occasion. The BestDose model performed slightly better than the model in Tucuxi (ME = −0.13 ± 5.16 vs. −1.90 ± 6.99 mg/L, p < 0.001), but overall results were in agreement between the two models. A significant proportion of patients exhibited underexposure or overexposure to daptomycin after the initial dosage, which supports TDM. The two models may be useful for model-informed precision dosing.

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The Scottish model of vancomycin dosing and therapeutic drug monitoring improves both efficacy and safety of vancomycin therapy

Vnitřní lékařství ◽

10.36290/vnl.2018.098 ◽

2018 ◽

Vol 64 (7-8) ◽

pp. 717-724

Author(s):

Kristýna Zahálková ◽

Aleš Chrdle ◽

Olga Dvořáčková ◽

Marie Kašparová ◽

Magdalena Horníková ◽

...

Keyword(s):

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Therapeutic Drug ◽

Efficacy And Safety ◽

Vancomycin Therapy

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A Moving Target—Vancomycin Therapeutic Monitoring

Journal of the Pediatric Infectious Diseases Society ◽

10.1093/jpids/piaa078 ◽

2020 ◽

Vol 9 (4) ◽

pp. 474-478

Author(s):

Alaina N Burns ◽

Jennifer L Goldman

Keyword(s):

Clinical Practice ◽

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Clinical Care ◽

Area Under The Curve ◽

Therapeutic Monitoring ◽

Therapeutic Drug ◽

Moving Target ◽

Efficacy And Safety ◽

Vancomycin Trough

Abstract Therapeutic drug monitoring (TDM) has been a common practice to optimize efficacy and safety of vancomycin. While vancomycin trough-only TDM has widely been integrated into pediatric clinical practice since 2009, recently updated vancomycin TDM guidelines published in March 2020 recommend area under the curve (AUC) based TDM for vancomycin instead of trough-only TDM. In this review, we discuss the rationale behind the change in TDM recommendations, describe two approaches for calculating vancomycin AUC in clinical practice, and address considerations for integrating vancomycin AUC TDM into pediatric clinical practice. Our primary goal is to provide pediatric clinicians with a resource for implementing vancomycin AUC monitoring into clinical care.

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Toolbox: Lithium therapeutic drug monitoring - Efficacy and safety parameters

Mental Health Clinician ◽

10.9740/mhc.n110675 ◽

2012 ◽

Vol 2 (1) ◽

pp. 3-5

Author(s):

Richard Silvia

Keyword(s):

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Therapeutic Drug ◽

Efficacy And Safety ◽

Safety Parameters

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Influence of model-predicted rivaroxaban exposure and patient characteristics on efficacy and safety outcomes in patients with acute coronary syndrome

Therapeutic Advances in Cardiovascular Disease ◽

10.1177/1753944719863641 ◽

2019 ◽

Vol 13 ◽

pp. 175394471986364 ◽

Cited By ~ 1

Author(s):

Liping Zhang ◽

Xiaoyu Yan ◽

Partha Nandy ◽

Stefan Willmann ◽

Keith A. A. Fox ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Coronary Syndrome ◽

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Patient Characteristics ◽

Therapeutic Drug ◽

Efficacy And Safety ◽

Additional Information ◽

Coronary Syndrome ◽

Exposure Response

Background: This analysis aimed to evaluate the impact of rivaroxaban exposure and patient characteristics on efficacy and safety outcomes in patients with acute coronary syndrome (ACS) and to determine whether therapeutic drug monitoring might provide additional information regarding rivaroxaban dose, beyond what patient characteristics provide. Methods: A post hoc exposure–response analysis was conducted using data from the phase III ATLAS ACS 2 Thrombolysis in Myocardial Infarction (TIMI) 51 study, in which 15,526 randomized ACS patients received rivaroxaban (2.5 mg or 5 mg twice daily) or placebo for a mean of 13 months (maximum follow up: 31 months). A multivariate Cox model was used to correlate individual predicted rivaroxaban exposures and patient characteristics with time-to-event clinical outcomes. Results: For the incidence of myocardial infarction (MI), ischemic stroke, or nonhemorrhagic cardiovascular death, hazard ratios (HRs) for steady-state maximum plasma concentration (Cmax) in the 5th and 95th percentiles versus the median were statistically significant but close to 1 for both rivaroxaban doses. For TIMI major bleeding events, a statistically significant association was observed with Cmax [HR, 1.08; 95% CI, 1.06–1.11 (95th percentile versus median, 2.5 mg twice daily)], sex [HR, 0.56; 95% CI, 0.38–0.84 (female versus male)], and previous revascularization [HR, 0.62; 95% CI, 0.44–0.87 (no versus yes)]. Conclusions: The shallow slopes of the exposure–response relationships and the lack of a clear therapeutic window render it unlikely that therapeutic drug monitoring in patients with ACS would provide additional information regarding rivaroxaban dose beyond that provided by patient characteristics.

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