Unit:
Κατεύθυνση Κλινική ΦαρμακευτικήLibrary of the School of Science
Author:
Peraki Aikaterini
Supervisors info:
ΒΑΛΣΑΜΗ ΓΕΩΡΓΙΑ, ΚΑΘΗΓΗΤΡΙΑ, ΤΜΗΜΑ ΦΑΡΜΑΚΕΥΤΙΚΗΣ, ΕΚΠΑ
ΜΑΡΚΑΝΤΩΝΗ-ΚΥΡΟΥΔΗ ΣΟΦΙΑ, ΚΑΘΗΓΗΤΡΙΑ, ΤΜΗΜΑ ΦΑΡΜΑΚΕΥΤΙΚΗΣ, ΕΚΠΑ
ΔΟΚΟΥΜΕΤΖΙΔΗΣ ΑΡΙΣΤΕΙΔΗΣ, ΕΠΙΚΟΥΡΟΣ ΚΑΘΗΓΗΤΗΣ, ΤΜΗΜΑ ΦΑΡΜΑΚΕΥΤΙΚΗΣ, ΕΚΠΑ
Original Title:
Αναδρομική Μελέτη της Ενδοφλέβιας Ιτρακοναζόλης στην Αντιμετώπιση Συστηματικών Μυκητιάσεων: Ανάγκη για Θεραπευτική Παρακολούθηση και Εξατομίκευση της Δοσολογίας
Translated title:
Retrospective Study of Intravenous Itraconazole in Treating Invasive Fungal Infections: Need for Therapeutic Drug Monitoring and Individual Modifications to the Administeres Dose
Summary:
Invasive fungal infections remain an unsolved problem because of the difficulties involved in their diagnosis and treatment. Severely ill patients in intensive care units (ICU) are frequently at risk of developing fungal infections. This has led to the empirical prescription of antifungal agents when the initial antibiotic treatment fails.
In ICU patients, the most common types of Candida infections are bloodstream infections, catheter-related infections, intra-abdominal infections and urinary tract infections. Together with Candida colonizations that are induced by profound alterations of the endogenous flora resulting from prolonged broad-spectrum antibiotic therapy and a loss of integrity of skin and mucosal barriers, surgery, total parenteral nutrition, acute renal failure, hemodialysis and treatment with immunosuppressive agents are major risk factors for invasive Candida spp. Infections.
Candida spp. and Aspergillus spp. are associated with high morbidity and mortality. Until recently, Candida albicans was by far the predominant species. However, a shift toward non-albicans Candida spp., such as C. glabrata and C. krusei, which have a reduced susceptibility to commonly used antifungal agents, was recently observed. Therefore, the early initiation of appropriate antifungal therapy is essential for reducing morbidity and mortality from invasive fungal infections in critical care medicine.
Itraconazole is a first-generation synthetic triazole antifungal that has been in clinical use for nearly two decades. Although fungistatic against pathogenic yeast, itraconazole retains activity against a portion of fluconazole-resistant isolates and demonstrates fungicidal activity against a number of filamentous organisms that cause severe invasive disease.
Compared to other members of its class, itraconazole demonstrates a number of favorable pharmacokinetic characteristics, including a protracted half-life, extensive tissue distribution, and an active metabolite whose activity lies within a single twofold dilution of the parent.
The development of an oral solution which makes use of hydroxypropyl-β-cyclodextrin (HP-β-CD) as a solubilizing agent has, in part, remedied the less-than-ideal bioavailability profile of the innovator capsule. However, the systemic availability with oral administration remains restricted to less than 60% of the administered dose. More recently, an intravenous formulation of itraconazole has been licensed for use. The availability of a parenteral product affords the opportunity to bypass significant presystemic clearance and achieve higher concentrations earlier in the course of treatment. It offers a means to administer drug to populations where oral formulations are impractical and also simplifies weight-based administration for pediatric patients.
Population pharmacokinetics can be defined as the study of the variability in plasma drug concentrations between individuals when standard dosage regimens are administered to different people belonging to a group of patients under examination.
In general, it is important for the factors contributing to this variability to be defined and quantified, so as to estimate their effect for the final pharmacodynamic result and consequently for the necessary individual modifications to the administered dose, depending on the patient’s needs.
One of the most important applications of the population pharmacokinetics to the clinical practice is the therapeutic drug monitoring.
The evidence for the potential clinical benefits of TDM for patients receiving itraconazole is strong, but largely circumstantial. TDM should be considered in the majority of patients receiving itraconazole for both invasive and allergic disease.
Main subject category:
Science
Keywords:
itraconazole, triazole, antifungal agent, intravenous, invasive fungal infections, intensive care units, population pharmacokinetics, therapeutic drug monitoring
Number of references:
194
File:
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ΔΙΠΛΩΜΑΤΙΚΗ ΠΕΡΑΚΗ.pdf
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