Investigation of Saliva as an Alternative to Plasma Monitoring of Voriconazole

Vanstraelen, Kim; Maertens, Johan; Augustijns, Patrick; Lagrou, Katrien; Loor, Henriëtte de; Mols, Raf; Annaert, Pieter; Malfroot, Anne; Spriet, Isabel

doi:10.1007/s40262-015-0269-z

Cited by 17 publications

(23 citation statements)

References 36 publications

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“…In addition, dried blood spot sampling can be performed for voriconazole and posaconazole TDM. Voriconazole saliva concentrations have also been examined as an alternative, easily collected specimen [70,71]. When implemented in clinical practice, these alternative sampling methods may be a more acceptable and less invasive sampling method for outpatient monitoring of older patients [57].…”

Section: Therapeutic Drug Monitoringmentioning

confidence: 99%

Strategies to Improve Medication Adherence in Older Persons: Consensus Statement from the Senior Italia Federanziani Advisory Board

et al. 2016

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Candida infections in the elderly are an important and expanding clinical problem, with significantly higher mortality in this group than in younger patients. The increasing problem of invasive Candida infections may be related to higher prevalence of immunocompromised older people and the emergence of treatment resistance. Older people, especially the frail and critically ill, are at higher risk of medication-related harmful effects due to changes in pharmacokinetics and pharmacodynamics, which may be further complicated by organ dysfunction, diminished homeostatic control, co-morbidities and polypharmacy. Here, we review the available options for the treatment of Candida infections and provide insights into the challenges surrounding the optimal use of antifungal drugs in the elderly. Key PointsCandida infections are a growing problem in elderly patients, with significant mortality in this group.Treatment in the elderly requires careful consideration of benefit and harm in the selection of both the drug and dose regimen.Therapeutic drug monitoring can be recommended for selected antifungal agents.

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Section: Therapeutic Drug Monitoringmentioning

confidence: 99%

Strategies to Improve Medication Adherence in Older Persons: Consensus Statement from the Senior Italia Federanziani Advisory Board

et al. 2016

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“…The ratios in the studies were based on AUC 0-12, C min (trough) or concentrations at multiple timepoints during dosing interval. The majority of studies reported significant correlation between saliva and plasma concentrations (r = 0.89 to 1.08, p < 0.0001 or < 0.001) in both adults (Purkins et al, 2002;Vanstraelen et al, 2015) and children (Michael et al, 2010). Vanstraelen et al observed improved linear correlation for free voriconazole concentration (S/P ratio 0.49 ± 0.03, r = 0.970, p < 0.001), compared with total drug concentration.…”

Section: Voriconazolementioning

confidence: 99%

“…From the four studies investigating saliva PK of voriconazole, two studies were conducted in healthy volunteers (Purkins et al, 2002;Purkins et al, 2003), one study in adult patients (Vanstraelen et al, 2015), and one study in adult and pediatric patients (Michael et al, 2010) (Table 2). Voriconazole dose in adults ranged from 3-5 mg/kg po (tablet or capsules) or iv twice daily with or without loading, and 7 mg/kg iv twice daily in children.…”

Section: Voriconazolementioning

confidence: 99%

Saliva for Precision Dosing of Antifungal Drugs: Saliva Population PK Model for Voriconazole Based on a Systematic Review.

et al. 2020

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Precision dosing for many antifungal drugs is now recommended. Saliva sampling is considered as a non-invasive alternative to plasma sampling for therapeutic drug monitoring (TDM). However, there are currently no clinically validated saliva models available. The aim of this study is firstly, to conduct a systematic review to evaluate the evidence supporting saliva-based TDM for azoles, echinocandins, amphotericin B, and flucytosine. The second aim is to develop a saliva population pharmacokinetic (PK) model for eligible drugs, based on the evidence. Databases were searched up to July 2019 on PubMed ® and Embase ® , and 14 studies were included in the systematic review for fluconazole, voriconazole, itraconazole, and ketoconazole. No studies were identified for isavuconazole, posaconazole, flucytosine, amphotericin B, caspofungin, micafungin, or anidulafungin. Fluconazole and voriconazole demonstrated a good saliva penetration with an average S/P ratio of 1.21 (± 0.31) for fluconazole and 0.56 (± 0.18) for voriconazole, both with strong correlation (r = 0.89-0.98). Based on the evidence for TDM and available data, population PK analysis was performed on voriconazole using Nonlinear Mixed Effects Modeling (NONMEM 7.4). 137 voriconazole plasma and saliva concentrations from 11 patients (10 adults, 1 child) were obtained from the authors of the included study. Voriconazole pharmacokinetics was best described by one-compartment PK model with first-order absorption, parameterized by clearance of 4.56 L/h (36.9% CV), volume of distribution of 60.7 L, absorption rate constant of 0.858 (fixed), and bioavailability of 0.849. Kinetics of the voriconazole distribution from plasma to saliva was identical to the plasma kinetics, but the extent of distribution was lower, modeled by a scale factor of 0.5 (4% CV). A proportional error model best accounted for the residual variability. The visual and simulation-based model diagnostics confirmed a good predictive performance of the

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“…For this reason, non-invasive samples for TDM are desirable. Vanstraelen et al developed a method for the determination of voriconazole in saliva samples [ 82 ]. The authors compared results obtained for saliva samples with those obtained for plasma samples.…”

Section: Antifungal Drugsmentioning

confidence: 99%

“…The identity lines are presented as dashed lines, and the regression lines are depicted as solid lines. In panel ( b ), the dashed–dotted line represents the regression line when total plasma voriconazole concentrations above 10 mg/L are excluded [ 82 ].…”

Section: Figurementioning

confidence: 99%

Review of Chromatographic Methods Coupled with Modern Detection Techniques Applied in the Therapeutic Drugs Monitoring (TDM)

Tuzimski

Petruczynik

2020

Molecules

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Therapeutic drug monitoring (TDM) is a tool used to integrate pharmacokinetic and pharmacodynamics knowledge to optimize and personalize various drug therapies. The optimization of drug dosing may improve treatment outcomes, reduce toxicity, and reduce the risk of developing drug resistance. To adequately implement TDM, accurate and precise analytical procedures are required. In clinical practice, blood is the most commonly used matrix for TDM; however, less invasive samples, such as dried blood spots or non-invasive saliva samples, are increasingly being used. The choice of sample preparation method, type of column packing, mobile phase composition, and detection method is important to ensure accurate drug measurement and to avoid interference from matrix effects and drug metabolites. Most of the reported procedures used liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) techniques due to its high selectivity and sensitivity. High-performance chromatography with ultraviolet detection (HPLC-UV) methods are also used when a simpler and more cost-effective methodology is desired for clinical monitoring. The application of high-performance chromatography with fluorescence detection (HPLC-FLD) with and without derivatization processes and high-performance chromatography with electrochemical detection (HPLC-ED) techniques for the analysis of various drugs in biological samples for TDM have been described less often. Before chromatographic analysis, samples were pretreated by various procedures—most often by protein precipitation, liquid–liquid extraction, and solid-phase extraction, rarely by microextraction by packed sorbent, dispersive liquid–liquid microextraction. The aim of this article is to review the recent literature (2010–2020) regarding the use of liquid chromatography with various detection techniques for TDM.

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Investigation of Saliva as an Alternative to Plasma Monitoring of Voriconazole

Abstract: Saliva can serve as a reliable alternative to plasma in voriconazole TDM, and it can easily be implemented in clinical practice.

Cited by 17 publications

References 36 publications

Strategies to Improve Medication Adherence in Older Persons: Consensus Statement from the Senior Italia Federanziani Advisory Board

Strategies to Improve Medication Adherence in Older Persons: Consensus Statement from the Senior Italia Federanziani Advisory Board

Saliva for Precision Dosing of Antifungal Drugs: Saliva Population PK Model for Voriconazole Based on a Systematic Review.

Review of Chromatographic Methods Coupled with Modern Detection Techniques Applied in the Therapeutic Drugs Monitoring (TDM)

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