scholarly journals Therapeutic Drug Monitoring of Isavuconazole: Serum Concentration Variability and Success Rates for Reaching Target in Comparison with Voriconazole

Antibiotics ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 487
Author(s):  
Malene Risum ◽  
Mai-Britt Vestergaard ◽  
Ulla Møller Weinreich ◽  
Marie Helleberg ◽  
Nadja Hawwa Vissing ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Serum Concentration ◽  
Therapeutic Range ◽  
Drug Monitoring ◽  
Therapeutic Index ◽  
Fluorescent Detection ◽  
Therapeutic Drug ◽  
Serum Concentrations ◽  
Success Rates ◽  
Off Label

Isavuconazole (ISZ) is used in the treatment of aspergillosis and mucormycosis. The purpose of this study was to evaluate the therapeutic drug monitoring (TDM) of ISZ samples from a clinical setting performed at Statens Serum Institut. Materials/methods: Isavuconazole serum concentrations were determined by fluorescent detection on a UHPLC. Serum-ISZ (s-ISZ) results were included and compared to those of serum-voriconazole (s-VRZ) in a 33 month period from March 2017. Clinical data were obtained for patients receiving ISZ. The therapeutic range was initially 2–10 mg/L, but was adjusted to 2–5 mg/L during the study period except for selected patients with Mucorales infections who received off-label doses of ISZ. Results: A total of 273 s-ISZ and 1242 s-VRZ measurements from 35 and 283 patients, respectively, were included. Seventeen patients had received both ISZ and VRZ with TDM within the study period. The median s-ISZ was 4.3 mg/L (0.5–15.4 mg/L) with 83% of measurements within the therapeutic index. The median s-VRZ was 2.6 mg/L (0.2–21.9 mg/L) with 67% of measurements within the therapeutic index. The median intra-/interindividual coefficient of variation (CV) was 43.4%/54.8% for ISZ compared to 53.2%/83.3% for VRZ. For patients receiving ISZ, the adverse events were mostly gastroenteric and few drug–drug interactions were observed. Furthermore, immediate change from ISZ to VRZ treatment seemed to lead to prolonged metabolism of ISZ with detection up to 35 days after discontinuation. Conclusions: The majority of patients achieved s-ISZ levels well within the therapeutic range with less intra/interindividual CV than patients receiving VRZ.

Is There a Role for Therapeutic Drug Monitoring of Anti-TNF Monoclonal Antibodies in Inflammatory Bowel Disease

2015 ◽  
Vol 33 (Suppl. 1) ◽  
pp. 70-77 ◽  
Author(s):  
Filip Baert
Keyword(s):  
Monoclonal Antibodies ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Treatment Guidelines ◽  
Therapeutic Drug ◽  
Serum Concentrations ◽  
Short Term ◽  
Clear Dose Response ◽  
Inflammatory Bowel

In recent years it has become clear that therapeutic drug monitoring can be an important tool to optimize outcome and costs of anti TNF treatment including the subcutaneous and fully human monoclonal antibodies. There is a clear dose response curve between early serum concentrations of all monoclonal antibodies and response both short term and long term. The wide variations in early serum concentrations are insufficiently explained by classic pharmacokinetic factors. Low early concentrations can lead to anti-drug antibody formation and ensuing loss of response. Therapeutic drug monitoring allows to rationalize the current practice of dose optimization and the use of concomitant immunomodulator treatment. However more prospective studies are needed before strong recommendations can enter treatment guidelines.

scholarly journals Antibiotic therapeutic drug monitoring in intensive care patients treated with different modalities of extracorporeal membrane oxygenation (ECMO) and renal replacement therapy: a prospective, observational single-center study

Critical Care ◽  
2020 ◽  
Vol 24 (1) ◽  
Author(s):  
Dennis Kühn ◽  
Carlos Metz ◽  
Frederik Seiler ◽  
Holger Wehrfritz ◽  
Sophie Roth ◽  
...  
Keyword(s):  
Intensive Care ◽  
Renal Replacement Therapy ◽  
Therapeutic Drug Monitoring ◽  
Extracorporeal Membrane Oxygenation ◽  
Replacement Therapy ◽  
Drug Monitoring ◽  
Therapeutic Drug ◽  
Serum Concentrations ◽  
Icu Patients ◽  
Intensive Care Patients

Abstract Background Effective antimicrobial treatment is key to reduce mortality associated with bacterial sepsis in patients on intensive care units (ICUs). Dose adjustments are often necessary to account for pathophysiological changes or renal replacement therapy. Extracorporeal membrane oxygenation (ECMO) is increasingly being used for the treatment of respiratory and/or cardiac failure. However, it remains unclear whether dose adjustments are necessary to avoid subtherapeutic drug levels in septic patients on ECMO support. Here, we aimed to evaluate and comparatively assess serum concentrations of continuously applied antibiotics in intensive care patients being treated with and without ECMO. Methods Between October 2018 and December 2019, we prospectively enrolled patients on a pneumological ICU in southwest Germany who received antibiotic treatment with piperacillin/tazobactam, ceftazidime, meropenem, or linezolid. All antibiotics were applied using continuous infusion, and therapeutic drug monitoring of serum concentrations (expressed as mg/L) was carried out using high-performance liquid chromatography. Target concentrations were defined as fourfold above the minimal inhibitory concentration (MIC) of susceptible bacterial isolates, according to EUCAST breakpoints. Results The final cohort comprised 105 ICU patients, of whom 30 were treated with ECMO. ECMO patients were significantly younger (mean age: 47.7 vs. 61.2 years; p < 0.001), required renal replacement therapy more frequently (53.3% vs. 32.0%; p = 0.048) and had an elevated ICU mortality (60.0% vs. 22.7%; p < 0.001). Data on antibiotic serum concentrations derived from 112 measurements among ECMO and 186 measurements from non-ECMO patients showed significantly lower median serum concentrations for piperacillin (32.3 vs. 52.9; p = 0.029) and standard-dose meropenem (15.0 vs. 17.8; p = 0.020) in the ECMO group. We found high rates of insufficient antibiotic serum concentrations below the pre-specified MIC target among ECMO patients (piperacillin: 48% vs. 13% in non-ECMO; linezolid: 35% vs. 15% in non-ECMO), whereas no such difference was observed for ceftazidime and meropenem. Conclusions ECMO treatment was associated with significantly reduced serum concentrations of specific antibiotics. Future studies are needed to assess the pharmacokinetic characteristics of antibiotics in ICU patients on ECMO support.

scholarly journals Optimum Use of Therapeutic Drug Monitoring and Pharmacokinetics-Pharmacodynamics in the NICU

2009 ◽  
Vol 14 (2) ◽  
pp. 66-74
Author(s):  
Peter Gal
Keyword(s):  
Drug Therapy ◽  
Therapeutic Drug Monitoring ◽  
Antiepileptic Drugs ◽  
Therapeutic Range ◽  
Drug Monitoring ◽  
Population Based ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Drug ◽  
Patient Response ◽  
Drug Concentrations

Therapeutic drug monitoring is increasingly giving way to dosing drugs based on population-based pharmacokinetic parameters, even when pharmacokinetic values vary quite a bit in individual patients. Further, drug concentrations are often considered appropriate if they are within a defined therapeutic range, even if the patient response is suboptimal. This lecture discusses the limitations of therapeutic ranges in neonates, and proposes greater emphasis on pharmacodynamic curves to individualize drug therapy. Examples are provided using methylxanthines, indomethacin, antiepileptic drugs and aminoglycosides. The potential to use pharmacokinetic findings to describe physiologic changes and occasionally assist with diagnosis is also discussed.

scholarly journals Therapeutic Drug Monitoring of Voriconazole in AIDS Patients

2021 ◽  
Author(s):  
Tingting Chen ◽  
Zhiqiang Lin ◽  
Huatang Zhang ◽  
Qingquan Zhang ◽  
Limian Hong ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Interactions ◽  
Therapeutic Range ◽  
Trough Concentration ◽  
Drug Monitoring ◽  
Linear Regression Analysis ◽  
Immune Deficiency Syndrome ◽  
Therapeutic Drug ◽  
Affecting Factors ◽  
Aids Patients

Abstract Background The safety and efficacy of Voriconazole in Acquired Immune Deficiency Syndrome (AIDS) patients is difficult to guarantee. In this study, Therapeutic Drug Monitoring (TDM) of Voriconazole in AIDS patients was investigated with the aim to further verify the significance of voriconazole TDM in AIDS patients and to explore more strategies to improve individualized medication. Methods The data of AIDS patients who underwent voriconazole TDM in our hospital from May 2018 to August 2021 were collected. The basic information of patients, the results of voriconazole TDM, the individualized intervention, the affecting factors of voriconazole concentration were analyzed, as well as the relationship between voriconazole trough concentration and safety. Results A total of 46 tests of voriconazole TDM were performed in 28 AIDS patients. Only 57.14% patients reached the therapeutic range at first TDM, and 87.50% patients reached the therapeutic range after intervention based on first TDM. 21.43% patients develop voriconazole-related Adverse Drug Reactions (ADRs), and ADRs were mostly occurred when voriconazole concentration is above 5.0 µg/mL. Spearman correlation coefficient rs was calculated to be 0.729 for voriconazole trough concentration and the incidence of ADRs, exhibiting a significant, positive linear correlation (P=0. 017). 50% patients had polypharmacy and drug interactions are common. For example, rifampicin can significantly reduce the plasma concentration of voriconazole. Multiple linear regression analysis showed Hypoproteinemia was a significant factor affecting voriconazole trough concentration(P=0.006). Conclusion AIDS patients usually have a low attainment rate of voriconazole trough concentration after initiation of standard dosing regimen. The affecting factors seem multifactorial and complex, of which hypoproteinemia is of great significance. Meanwhile, we need to be alert to the effects of drug interactions. The incidence of voriconazole related ADRs is high, mostly occurring when voriconazole concentration is above 5.0 µg/mL. Therefore, TDM can provide meaningful guidance for dosage optimization of voriconazole, and the dosage adjustment method in Chinese Guideline is applicable for the population of AIDS patients.

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