Therapeutic drug monitoring for triazoles

Hope, William; Billaud, Éliane; Lestner, Jodi M.; Denning, David W.

doi:10.1097/qco.0b013e3283184611

Cited by 134 publications

(98 citation statements)

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“…Considering that almost all fungal pathogens isolated during posaconazole PAP were susceptible in vitro to the triazole (unreported data), the possibility of reduced absorption, with sub-therapeutic serum concentrations of posaconazole, must be considered. [23][24][25] Many factors, such as the development of mucositis, impaired dietary intake and use of proton pump inhibitors may cause interindividual pharmacokinetic variability in AML patients, and therapeutic drug monitoring may be required. [23][24][25][26][27][28] Unlike previous studies showing impaired sensitivity of the GM assay in patients on antifungal therapy, 29 in our experience GM retained a major role in the diagnosis of IA also in patients receiving posaconazole.…”

Section: *Three Patients With a Diagnosis Of Invasive Aspergillosis Wmentioning

confidence: 99%

Posaconazole prophylaxis during front-line chemotherapy of acute myeloid leukemia: a single-center, real-life experience

et al. 2011

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The online version of this article has a Supplementary Appendix. BackgroundPosaconazole is effective as primary antifungal prophylaxis of invasive fungal diseases in patients with acute myeloid leukemia. Design and MethodsThe impact of primary antifungal prophylaxis administered during front-line chemotherapy for acute myeloid leukemia was evaluated by comparing 58 patients who received oral amphotericin B (control group) to 99 patients who received oral posaconazole (posaconazole group). The primary endpoint was the incidence of proven/probable invasive fungal diseases. Secondary endpoints included incidence of invasive aspergillosis, survival at 4 and 12 months after the diagnosis of acute myeloid leukemia and costs. ResultsProven/probable invasive fungal diseases were documented in 51.7% of patients in the control group and in 23.2% in the posaconazole group (P=0.0002). Invasive aspergillosis was documented in 43% of patients in the control group and in 15% in the posaconazole group (P=0.002). No survival difference was observed in patients aged over 60 years. In patients aged 60 years or less, a statistically significant survival advantage was observed at 4 months, but no longer at 12 months, in the posaconazole group (P=0.03). It was calculated that in the posaconazole group there was a mean 50% cost reduction for the antifungal drugs. ConclusionsPrimary antifungal prophylaxis with posaconazole during front-line chemotherapy was effective in preventing invasive fungal diseases in a "real-life" scenario of patients with acute myeloid leukemia, resulted in an early but transitory survival advantage in younger patients and was economically advantageous.

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Section: *Three Patients With a Diagnosis Of Invasive Aspergillosis Wmentioning

confidence: 99%

Posaconazole prophylaxis during front-line chemotherapy of acute myeloid leukemia: a single-center, real-life experience

et al. 2011

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“…Patients data are reported in table 3, divided by sex. VRC C trough ranged from 0 to 7 µg/mL, while PSC C trough ranged from 0.08 to 2.06 µg/mL, according to data present in literature [6,8,11].…”

Section: Methods Validationmentioning

confidence: 78%

“…VRC exhibits ca.100-fold variability in drug levels in individuals receiving the same dose [6], showing non-linear saturable pharmacokinetics [7]. To our knowledge available recommendations suggest that VRC levels should be maintained > 1 g/mL and that levels > 5.5 g/mL have been reported to be possibly associated with toxicity [8].…”

Section: Patientsmentioning

confidence: 99%

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A New HPLC Validated Method for Therapeutic Monitoring Of Triazoles in Human Plasma: First Results in Leukaemic Patients

Francia

Cardalana²,

P³

et al. 2015

Clin Exp Pharmacol

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Therapeutic drug monitoring of triazoles is widely used in clinical practice to optimize therapy, especially in those patients who need antifungal treatment as co-medications. Here it is described development and validation of a new chromatographic method in order to quantify voriconazole and posaconazole in human plasma by ultraviolet detection.After liquid extraction of analytes from plasma using acetonitrile, samples are evaporated to dryness and then reconstituted in mobile phase for chromatographic separation. Analysis is achieved on C18 reverse phase column and eluate is monitored at 250 nm. Mobile phase consisted of 35% water, 15% methanol, 50% acetonitrile. Flavone was used as internal standard; retention times (minutes) were, respectively, for voriconazole 3.9, posaconazole 7.9, flavone 7.1.Accuracy and variability were assayed by inter-and intra-day validation, conducted on three separate days. Methodology was used for the analysis of plasma samples of acute myeloid leukaemia patients in therapy with voriconazole or posaconazole for treatment of fungal infections, in order to perform therapeutic monitoring of antifungal drugs levels.Mean inter-and intra-day accuracy and variability were acceptable for both compounds; thus, method developed resulted linear in the range 0.125-8 µg/mL. Limits of quantification and limits of detection for voriconazole and posaconazole are, respectively, 0.100 and 0.050 µg/mL, and 0.030 and 0.020 µg/mL.It has been observed that voriconazole and posaconazole circulating levels achieved in patients are on average below the therapeutic range defined in literature.In conclusion, method developed and validated in order to quantify voriconazole and posaconazole in human plasma is accurate and precise; it is easily applicable and reproducible, and, therefore, it could be an useful tool in clinical routine to better manage patients in case of multi-therapy approach.

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“…8, [25][26][27][28][29][30][31][32] In their recent review articles, Smith and others 33 and Hope and others 34 addressed the topic of TDM for antifungal agents, discussing voriconazole briefly. Brüggemann and others 35 and Howard and others 36 also discussed the role of TDM for voriconazole specifically, the latter focusing exclusively on invasive aspergillosis.…”

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confidence: 99%

Role of Therapeutic Drug Monitoring of Voriconazole in the Treatment of Invasive Fungal Infections

Kuo

Ensom

2009

CJHP

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Background: Voriconazole is a broad-spectrum, second-generation triazole antifungal agent with demonstrated efficacy in the treatment of invasive fungal infections caused by Aspergillus spp. and Candida spp. Given the characteristically poor prognosis of patients with invasive fungal infections and the protracted duration of treatment required, therapeutic monitoring of voriconazole is, in theory, an attractive method to optimize antifungal therapy. Objective:To determine the utility of therapeutic drug monitoring for voriconazole. Methods:A previously published decision-making algorithm was used to assess the currently available literature on therapeutic drug monitoring of voriconazole.Results: Several analytical methods can be used to quantify plasma or serum concentrations of voriconazole. Reasons for therapeutic monitoring of this drug include wide variability both within and between individuals secondary to drug properties, drug-drug interactions, and disease states. Furthermore, voriconazole follows nonlinear pharmacokinetics with saturable hepatic clearance. Another potential factor in favour of therapeutic drug monitoring for voriconazole is genetic polymorphism of CYP2C19, whereby patients who are homozygous for poor metabolism (about 19% of non-Indian Asians) can have 4-fold greater exposure to voriconazole. The concentrations of this drug are also greater in patients with hepatic impairment. Drug-drug interactions with other substrates of CYP2C9, CYP2C19, and CYP3A4 can also alter voriconazole concentrations. However, the correlations between plasma concentrations of voriconazole and its efficacy and toxicity are not well defined. Although lower and upper target thresholds of 0.25-2 mg/L and 4-6 mg/L, respectively, have been suggested, studies to date have not been appropriately designed or powered to reveal any definitive association. Conclusions:Routine therapeutic drug monitoring of voriconazole is not recommended except in certain circumstances, such as lack of response to therapy or evidence of toxicity, in which case selective monitoring of voriconazole concentrations may be of clinical utility. Méthodes : Un algorithme de prise de décision publié a été utilisé pour évaluer la documentation actuellement disponible sur le suivi thérapeutique pharmacologique du voriconazole. Résultats :Plusieurs méthodes analytiques peuvent servir à quantifier les concentrations sériques ou plasmatiques de voriconazole. Les raisons de recourir au suivi thérapeutique pharmacologique de ce médicament sont notamment la grande variabilité intra et interindividuelle attribuable aux propriétés du médicament, aux interactions médicament-médicament et aux affections. De plus, le voriconazole a un comportement pharmacocinétique non linéaire en raison d'une clairance hépatique saturable. Un autre facteur potentiellement en faveur du suivi thérapeutique pharmacologique du voriconazole est le polymorphisme génétique du CYP2C19 qui, chez les patients homozygotes ayant un faible métabolisme (environ 19 % des Asiatiques ...

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Therapeutic drug monitoring for triazoles

Abstract: Therapeutic drug monitoring represents an important mechanism to optimize the outcome of immunocompromised patients receiving triazoles.

Cited by 134 publications

References 62 publications

Posaconazole prophylaxis during front-line chemotherapy of acute myeloid leukemia: a single-center, real-life experience

Posaconazole prophylaxis during front-line chemotherapy of acute myeloid leukemia: a single-center, real-life experience

A New HPLC Validated Method for Therapeutic Monitoring Of Triazoles in Human Plasma: First Results in Leukaemic Patients

Role of Therapeutic Drug Monitoring of Voriconazole in the Treatment of Invasive Fungal Infections

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