For the determination of fluconazole (FLU) oxidation stability under permanganate treatment at the acidic pH, a sensitive, reproducible, and stability-indicating ultra-performance liquid chromatography–mass spectrometry (UPLC/MS) method was developed. Three additional products (tR = 5.79, 6.98, 7.54) were observed besides the FLU (tR = 6.22). The proposed method was used to study the kinetics of FLU oxidative degradation. An oxidation process followed kinetics of the second-order reaction. The degradation rate constant and the corresponding half-life obtained for the FLU oxidative degradation were 0.5626 h-1 and 16.69 h, respectively. The putative oxidation products were characterized and their fragmentation pathways, on a basis of MS/MS data, were proposed.
Medicinal nail lacquers are the most effective topical treatment of nail diseases. These formulations generally are organic solutions of the active substance as well as film-forming polymer and plasticizer, which affects the characteristics of the film formed after application and solvent evaporation. The aim of this work was to test effects of plasticizer present in nail lacquer formulations on permeation kinetics of fluconazole through the bovine hoof membrane in a novel in vitro test. The formulations contained Eudragit RS100 dissolved in acetone, and dibutyl-phthalate, PEG 400 or propylene glycol as plasticizers present in two different concentrations. Permeation studies were carried out during 7-day period, and the obtained permeability profiles analyzed using similarity and difference factors, and by model dependent permeation kinetics. When analyzed within the same strength, the highest extent of fluconazole permeation was obtained from formulation with lower concentration of propylene glycol at 0.9% fluconazole concentration, while for formulations with 1.8% and 2.7% of fluconazole, the highest permeation was achieved from formulation with the higher content of PEG400. The permeation profiles showed greater difference within one formulation of different fluconazole content, than with the same plasticizer present in different concentrations, when using dibutyl-phthalate and PEG400. Permeation profiles were similar when using propylene glycol. When comparing formulations with the same concentration of plasticizers, there were differences in formulations with the higher fluconazole concentrations. Permeation kinetics depended on fluconazole concentration as well as the path length the active substance had to pass to reach the receptor solution.
Candida albicans species is the most common yeast isolated from the candidiasis, however the number of fungal infections caused by non-albicans Candida (Candida glabrata, Candida tropicalis, Candida parapsilosis, Candida krusei) has increased in recent years. Fluconazole is an eff ective and well tolerated the antifungal azole drug with parenteral and oral forms. This agent directed to 14--demethylase lanosterol (the product of the ERG11 gene) – the enzyme important in the biosynthesis of ergosterol – the major constituent of fungal membranes. Antifungal drug resistance is associated with the molecular mechanisms, especially with the point mutations of the ERG11 gene and the expression of genes CDR1, CDR2, MDR1 encoding so called effl ux-pumps, the system of transport fl uconazole across the plasma membrane. The aim of this study was the review of the research in various medical centres and the evaluation of the susceptibility of Candida albicans strains and other Candida spp. to fluconazole. These strains obtained from the clinical samples of the patients hospitalized. The fluconazole activity against the yeasts isolates was evaluated in vitro using the reference methods according by the CLSI, predominantly by the broth dilution methods with the determination the minimum inhibitory concentration MIC. Here are the conclusions obtained on the basis of the presented research: 1. The isolates of Candida spp. showed diff erent levels of susceptibility to fluconazole. 2. It’s important to determine the susceptibility of Candida spp. to fluconazole before beginning of treatment to improve the treatment outcome.
PL
Candida albicans to najczęściej izolowany gatunek w przypadku kandydoz, jednakże liczba infekcji grzybiczych z udziałem non-albicans Candida (Candida glabrata, Candida tropicalis, Candida parapsilosis, Candida krusei) w ostatnich latach wyraźnie wzrosła. Flukonazol jest skutecznym i dobrze tolerowanym lekiem przeciwgrzybiczym – azolem, stosowanym w formie parenteralnej lub doustnej. Lek ten celuje w 14--demetylazę lanosterolu (produkt genu ERG11), enzym istotny w biosyntezie ergosterolu będącego głównym składnikiem błony komórkowej grzyba. Oporność na flukonazol jest związana z istnieniem molekularnych mechanizmów, szczególnie z punktowymi mutacjami w genie ERG11 i ekspresją genów CDR1,CDR2, MDR1 kodujących tzw. effl ux-pumps, tj. system transportu niezbędny do wyrzutu fl ukonazolu przez błonę komórkową. Celem niniejszej pracy było dokonanie przeglądu badań z różnych ośrodków medycznych, dotyczących oceny wrażliwości na fl ukonazol szczepów Candida albicans i innych Candida spp. wyizolowanych z materiałów klinicznych pobranych od hospitalizowanych pacjentów. Aktywność flukonazolu wobec izolatów drożdżaków była oceniana referencyjnymi metodami zgodnymi z zaleceniami CLSI, z przewagą metod rozcieńczeniowych, pozwalających na określenie minimalnego stężenia hamującego MIC. Na podstawie wyników analizowanych badań można sformułować następujące wnioski: 1. Kliniczne szczepy Candida spp. cechują się zróżnicowanym poziomem wrażliwości na flukonazol. 2. Istotne wydaje się oznaczanie wrażliwości Candida spp. na flukonazol przed rozpoczęciem leczenia, w celu uzyskania pozytywnych wyników terapii.
Candida is a yeast species recognized as the most frequent etiological agent of systemic and invasive thrush in humans. Invasions can affect all tissues, organs and systems of human in various stages of development. In the last 10 years Candida infections have increased 15 times. The purpose of our study was to determine the sensitivity of four antibiotics belonging to three different groups of antifungal agents against clinical and food-borne Candida strains. Our studies showed that of all tested strains, 7% was resistant to nystatin, 32% to fluconazole, 23% to voriconazole, and no strains grew in the presence of caspofungin. Despite the differences in biochemical profiles of clinical and food-borne isolates of Candida, a group of strains showing resistance to antibiotics include both types of isolates. At the same time circulating of antibiotic-resistant strains outside the hospital environment and the yeast infection via food is possible.
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