Utility of posaconazole therapeutic drug monitoring and assessment of plasma concentration threshold for effective prophylaxis of invasive fungal infections: a meta-analysis with trial sequential analysis

نویسندگان

  • Lu Chen
  • Yan Wang
  • Tao Zhang
  • Ying Li
  • Ti Meng
  • Leichao Liu
  • Ruifang Hao
  • Yalin Dong
چکیده

BACKGROUND Posaconazole therapeutic drug monitoring (TDM) is increasingly used in clinical practice. However, the utility of posaconazole TDM and the target of posaconazole plasma concentration for clinical successful prophylaxis remain uncertain and controversial. The aim of this study was to evaluate posaconazole exposure-response relationship and determine an optimum posaconazole concentration for prophylaxis against invasive fungal infections (IFIs). METHODS Bibliographic databases were searched (from inception to September 2017) to select studies including the clinical outcomes below and above concentration cut-off value of 0.5 mg/L and 0.7 mg/L. The reliability of the results were evaluated with trial sequential analysis (TSA). RESULTS Twenty-eight studies with 1930 patients included were analyzed. The results of our pooled analysis demonstrated that patients with posaconazole plasma concentrations over 0.5 mg/L were twice more likely to achieve successful responses compared with those with lower concentrations (odds ratio, OR = 1.98, 95% confidence interval, CI 1.09-3.58, P = 0.02) while the threshold, 0.7 mg/L showed no significant difference (OR = 1.84, 95% CI 0.94-3.63, P = 0.08). The TSA results showed that there was sufficient information to support these findings. CONCLUSIONS An optimal posaconazole concentration target of 0.5 mg/L is suggested to ensure the clinical prophylactic efficacy and may help reduce the dosage and dose-dependent toxicity comparing with the target of 0.7 mg/L.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Posaconazole exposure-response relationship: evaluating the utility of therapeutic drug monitoring.

Posaconazole has become an important part of the antifungal armamentarium in the prophylaxis and salvage treatment of invasive fungal infections (IFIs). Structurally related to itraconazole, posaconazole displays low oral bioavailability due to poor solubility, with significant drug interactions and gastrointestinal disease also contributing to the generally low posaconazole plasma concentratio...

متن کامل

Evaluation of Posaconazole Pharmacokinetics in Adult Patients with Invasive Fungal Infection

Mortality and morbidity due to invasive fungal infections have increased over the years. Posaconazole is a second-generation triazole agent with an extended spectrum of activity, which shows a high interindividual variability in its plasma levels, rendering dosing in many patients inconsistent or inadequate. Hence, posaconazole therapeutic drug monitoring, which is easily available in clinical ...

متن کامل

A Review of Antifungals and their Mono- and Combination- therapy in the Treatment of Invasive Fungal Infections

Invasive fungal infections with high mortality rate are a growing health concern in hospitals and medical centers. The infection usually occurs in people with compromised immune systems. The purpose of this paper is a review of the most commonly prescribed antifungal drugs for invasive fungal diseases. Antifungals consist of the four main groups; polyenes, azoles, echinocandins and DNA an...

متن کامل

Development, clinical utility, and place in therapy of posaconazole for prevention and treatment of invasive fungal infections

Posaconazole is an extended-spectrum azole antifungal that exhibits activity against a broad range of fungal pathogens, including yeasts and moulds. Clinical data have demonstrated the clinical utility of posaconazole against many therapy-refractory pathogens, including Aspergillus spp, Fusarium spp, and Zygomycetes. These data have provided clinicians with hope in these difficult situations. S...

متن کامل

A routine method for the quantification of the novel antimycotic drug posaconazole in plasma using liquid chromatography-tandem mass spectrometry.

BACKGROUND Posaconazole is now widely used for prophylaxis of invasive fungal infections in immunocompromised patients. The pharmacokinetic properties of the drug argue for therapeutic monitoring, but so far described analytical methods have shortcomings with respect to application in a routine setting. The aim of our work was to develop an analytical method suitable for routine use. METHODS ...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره 18  شماره 

صفحات  -

تاریخ انتشار 2018