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Itraconazole

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https://www.readbyqxmd.com/read/28940733/in-vitro-biofilms-and-antifungal-susceptibility-of-dermatophyte-and-non-dermatophyte-molds-involved-in-foot-mycosis
#1
Nourchéne Toukabri, Serena Corpologno, Marie-Elisabeth Bougnoux, Dalenda El Euch, Najla Sadfi-Zouaoui, Giovanna Simonetti
BACKGROUND: Tinea pedis and onychomycosis are among the commonest fungal diseases in the world. Dermatophytes and, less frequently, non-dermatophyte molds are etiological agents of foot mycosis and could be able to form biofilms. Fungal biofilm has demonstrated increasing drug resistance OBJECTIVES: This work aims to evaluate in vitro the ability to form biofilm and the susceptibility to antifungal drugs of sessile dermatophytes and non-dermatophyte molds involved in foot mycosis. Methods Thirty-six dermatophytes and non-dermatophyte molds isolated from Tunisian patients with foot mycoses, and identified with MALDI-TOF have been tested...
September 22, 2017: Mycoses
https://www.readbyqxmd.com/read/28928005/sensitive-and-selective-quantification-of-total-and-free-itraconazole-and-hydroxyitraconazole-in-human-plasma-using-ultra-performance-liquid-chromatography-coupled-to-tandem-mass-spectrometry
#2
Yosuke Suzuki, Ryota Tanaka, Nobuhiro Oyama, Ko Nonoshita, Kazuhiko Hashinaga, Kenji Umeki, Yuhki Sato, Kazufumi Hiramatsu, Jun-Ichi Kadota, Hiroki Itoh
OBJECTIVES: Protein-free (unbound) drug concentrations have been reported to be better biomarker of pharmacodynamics compared with total drug concentrations. In this study, we developed and validated an assay for the quantification of total and free itraconazole and hydroxyitraconazole, a main metabolite with antifungal activity, in human plasma using ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS). DESIGN & METHODS: Plasma sample was ultra-filtrated for the measurement of free itraconazole and hydroxyitraconazole concentrations...
September 16, 2017: Clinical Biochemistry
https://www.readbyqxmd.com/read/28927987/industry-perspective-on-contemporary-protein-binding-methodologies-considerations-for-regulatory-drug-drug-interaction-and-related-guidelines-on-highly-bound-drugs
#3
REVIEW
Li Di, Christopher Breen, Rob Chambers, Sean T Eckley, Robert Fricke, Avijit Ghosh, Paul Harradine, J Cory Kalvass, Stacy Ho, Caroline A Lee, Punit Marathe, Everett J Perkins, Mark Qian, Susanna Tse, Zhengyin Yan, Maciej J Zamek-Gliszczynski
Regulatory agencies have recently issued drug-drug interaction (DDI) guidelines, which require determination of plasma protein binding (PPB). To err on the conservative side, the agencies recommend that a 0.01 lower limit of fraction unbound (fu) be used for highly bound compounds (>99%), irrespective of the actual measured values. While this may avoid false negatives, the recommendation would likely result in a high rate of false positive predictions, resulting in unnecessary clinical studies and more stringent inclusion/exclusion criteria, which may add cost and time in delivery of new medicines to patients...
September 16, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28927025/repurposing-itraconazole-for-the-treatment-of-cancer
#4
Rachel Pounds, Sarah Leonard, Christopher Dawson, Sean Kehoe
The repurposing of drugs is becoming increasingly attractive as it avoids the lengthy process and cost implications associated with bringing a novel drug to market. Itraconazole is a broad-spectrum anti-fungal agent. An emerging body of in vivo, in vitro and clinical evidence have confirmed that it also possesses antineoplastic activities and has a synergistic action when combined with other chemotherapeutic agents. It acts via several mechanisms to prevent tumour growth, including inhibition of the Hedgehog pathway, prevention of angiogenesis, decreased endothelial cell proliferation, cell cycle arrest and induction of auto-phagocytosis...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28923874/agar-based-screening-for-azole-resistance-in-aspergillus-fumigatus-using-vipcheck%C3%A2-a-single-centre-evaluation
#5
J B Buil, H A L van der Lee, A J M M Rijs, J Zoll, J A M F Hovestadt, W J G Melchers, P E Verweij
Introduction Antifungal susceptibility testing is an essential tool for guiding therapy, although EUCAST and CLSI reference methods are often only available in specialized centres. We studied the performance of an agar-based screening method for the detection of azole resistance in Aspergillus fumigatus cultures.Methods The VIPcheck™ consists of four wells containing voriconazole, itraconazole, posaconazole or a growth control. Ninety-six A. fumigatus isolates were used. Thirty-three isolates harboured a known resistance mechanism: TR34/L98H (11 isolates); TR46/Y121F/T289A (6 isolates); TR53 (2 isolates) and fourteen isolates with other cyp51A-gene point mutations...
September 18, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28923863/synergistic-effects-of-tacrolimus-and-azoles-against-exophiala-dermatitidis
#6
Lujuan Gao, Yi Sun, Chengyan He, Tongxiang Zeng, Ming Li
In vitro interactions of tacrolimus, a calcineurin inhibitor, and azoles including itraconazole, voriconazole, and posaconazole against planktonic cells and biofilms of Exophiala dermatitidis were assessed via broth microdilution checkerboard technique. A total of 16 clinical isolates were studied. The results revealed favorable synergistic inhibitory activity between tacrolimus and itraconazole, voriconazole, or posaconazole against planktonic cells of E. dermatitidis However, limited synergism was observed against biofilms of E...
September 18, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28923766/development-of-stability-enhanced-ternary-solid-dispersions-via-combinations-of-hpmcp-and-soluplus-%C3%A2-processed-by-hot-melt-extrusion
#7
Ahmad B Albadarin, Catherine B Potter, Mark Davis, Javed Iqbal, Sachin Korde, Sudhir Pagire, Anant Paradkar, Gavin Walker
The aim of this study was to evaluate a novel combination of hydroxypropyl methylcellulose phthalate (HPMCP-HP-50) and Soluplus(®) polymers for enhanced physicochemical stability and solubility of the produced amorphous solid dispersions (ASDs). This was achieved using hot melt extrusion (HME) to convert the crystalline active pharmaceutical ingredient (API) into a more soluble amorphous form within the ternary systems. Itraconazole (ITZ), a Biopharmaceutics Classification System class II (BCS II) API, was utilized as the model drug...
September 15, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28923421/avoidance-of-food-effect-on-oral-absorption-profile-of-itraconazole-by-self-micellizing-solid-dispersion-approach
#8
Yoshiki Kojo, Kanako Kobayashi, Saori Matsunaga, Hiroki Suzuki, Yoshiki Seto, Hideyuki Sato, Satomi Onoue
The present study was aimed to avoid pharmacokinetic transitions of itraconazole (ITZ) evoked by high-fat meal intake by employing a self-micellizing solid dispersion (SMSD) approach. The dissolution behavior of SMSD/ITZ was assessed in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). To evaluate the food effect on the oral absorption profile of ITZ, a pharmacokinetic study was conducted on orally-dosed ITZ samples in fasted and high-fat meal-fed rats. Crystalline ITZ showed a 9.0-fold higher dissolution amount of ITZ in fed-state SGF (FeSSGF) than in fasted-state SGF (FaSSGF), whereas there was no significant difference in the dissolution amount of ITZ in SMSD/ITZ between FeSSGF and FaSSGF...
June 15, 2017: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28922604/a-comparative-study-on-the-performance-of-inert-and-functionalized-spheres-coated-with-solid-dispersions-made-of-two-structurally-related-antifungal-drugs
#9
Naila A Mugheirbi, Peter O'Connell, Dolores R Serrano, Anne Marie Healy, Lynne S Taylor, Lidia Tajber
Fluid bed coating offers potential advantages as a formulation platform for amorphous solid dispersions (ASDs) of poorly soluble drugs, being a one-step manufacturing process which could reduce the risk of phase separation associated with multiple step manufacturing approaches. However, the impact of the physicochemical nature of carrier spheres on the properties and drug release from the ASDs has not been studied in detail. In this work, tartaric acid (TAP) and microcrystalline cellulose (CEL) spheres were chosen as examples of functional and inert beads, respectively...
September 18, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28920790/pharmacokinetics-efficacy-and-safety-of-voriconazole-and-itraconazole-in-healthy-cottonmouths-agkistrodon-piscivorus-and-massasauga-rattlesnakes-sistrurus-catenatus-with-snake-fungal-disease
#10
Dana M Lindemann, Matthew C Allender, Marta Rzadkowska, Grace Archer, Lauren Kane, Eric Baitchman, Elizabeth A Driskell, Caroline T Chu, Kuldeep Singh, Shih-Hsuan Hsiao, John M Sykes, Sherry Cox
Snake fungal disease (SFD; Ophidiomyces ophiodiicola) is posing a significant threat to several free-ranging populations of pitvipers. Triazole antifungals have been proposed for the treatment of mycoses in reptiles; however, data are lacking about their safety and efficacy in snakes with SFD. Study 1 investigated in vitro susceptibility, and identified that plasma concentrations >250 ng/ml (voriconazole) and >1,000 ng/ml (itraconazole) may be effective in vivo for SFD. In Study 2, the pharmacokinetics after a single subcutaneous voriconazole injection were assessed in apparently healthy free-ranging cottonmouths (Agkistrodon piscivorus)...
September 2017: Journal of Zoo and Wildlife Medicine: Official Publication of the American Association of Zoo Veterinarians
https://www.readbyqxmd.com/read/28904931/isolation-of-candida-species-from-gastroesophageal-lesions-among-pediatrics-in-isfahan-iran-identification-and-antifungal-susceptibility-testing-of-clinical-isolates-by-e-test
#11
Fatemeh Salehi, Mehran Esmaeili, Rasoul Mohammadi
BACKGROUND: Candida species can become opportunistic pathogens causing local or systemic invasive infections. Gastroesophageal candidiasis may depend on the Candida colonization and local damage of the mucosal barrier. Risk factors are gastric acid suppression, diabetes mellitus, chronic debilitating states such as carcinomas, and the use of systemic antibiotics and corticosteroids. The aim of this study is collection and molecular identification of Candida species from gastroesophageal lesions among pediatrics in Isfahan, and determination of minimum inhibitory concentration (MIC) ranges for clinical isolates...
2017: Advanced Biomedical Research
https://www.readbyqxmd.com/read/28903066/development-of-fine-solid-crystal-suspension-with-enhanced-solubility-stability-and-aerosolization-performance-for-dry-powder-inhalation
#12
Ling Lin, Guilan Quan, Tingting Peng, Zhengwei Huang, Vikramjeet Singh, Ming Lu, Chuanbin Wu
Dry powder for inhalation (DPI) is an attractive approach for the treatment of local lung diseases. However, the application of drugs with poor water solubility is often limited due to the dissolution obstacles in the fluid layer of the lung lining. In this study, fine solid-crystal suspension (FSCS) was proposed as a solvent-free method to improve the solubility of a drug with poor solubility (itraconazole) and achieve high deposition efficiency simultaneously. The FSCS, in which the crystalline drug particle was highly dispersed in the crystalline excipient, was initially prepared as drug-excipient extrudate by hot melt extrusion, followed by jet milling into fine particles...
September 10, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28901803/in-vitro-activity-of-calcium-channel-blockers-in-combination-with-conventional-antifungal-agents-against-clinically-important-filamentous-fungi
#13
Mónika Homa, Kinga Hegedűs, Ádám Fülöp, Vanessza Wolfárt, Shine Kadaikunnan, Jamal M Khaled, Naiyf S Alharbi, Csaba Vágvölgyi, László Galgóczy
Despite the current therapeutic options, filamentous fungal infections are associated with high mortality rate especially in immunocompromised patients. In order to find a new potential therapeutic approach, the in vitro inhibitory effect of two antiarrhythmic agents, diltiazem and verapamil hydrochloride were tested against different clinical isolates of ascomycetous and mucoralean filamentous fungi. The in vitro combinations of these non-antifungal drugs with azole and polyene antifungal agents were also examined...
September 2017: Acta Biologica Hungarica
https://www.readbyqxmd.com/read/28900769/interface-scopulariopsis-gracilis-fungal-keratitis-following-descemet-s-stripping-automated-endothelial-keratoplasty-dsaek-with-a-contaminated-graft
#14
Craig Wilde, Marco Messina, Tara Moshiri, Susan E Snape, Senthil Maharajan
PURPOSE: To report for the first time a case of interface Scopulariopsis gracilis fungal keratitis following Descemet's stripping automated endothelial keratoplasty (DSAEK) with a contaminated graft. METHODS: A 57-year-old man with bilateral keratoconus and previous bilateral penetrating keratoplasties (PK) developed graft failure in association with marked corneal ectasia. He underwent a successful DSAEK. Unfortunately, a contaminated graft was transplanted and the following morning we were contacted by the eye bank to inform us a slow-growing fungus had been detected in the culture plates inoculated with dextran solution used to store the issued corneoscleral button...
September 12, 2017: International Ophthalmology
https://www.readbyqxmd.com/read/28893772/triazole-resistance-is-still-not-emerging-in-a-fumigatus-isolates-causing-invasive-aspergillosis-in-brazilian-patients
#15
Clara E Negri, Sarah S Gonçalves, Ana Cristina P Sousa, Maria Daniela Bergamasco, Marinês D V Martino, Flavio Queiroz-Telles, Valerio Rodrigues Aquino, Paulo de Tarso O Castro, Ferry Hagen, Jacques F Meis, Arnaldo L Colombo
Aspergillus fumigatus azole resistance has globally emerged as a health problem. We evaluated the in vitro antifungal susceptibility of 221 clinical A. fumigatus isolates according to CLSI. Sixty-one isolates exhibiting MIC at the epidemiological cut-off value (ECV) for itraconazole or above ECV for any triazole were checked for CYP51A mutations. No mutations were documented, even for four isolates (1.8%) with high voriconazole MICs, indicating that triazoles may be safely used to treat aspergillosis in Brazil...
September 11, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28889027/re-evaluating-the-presumed-superiority-of-amorphous-nanoparticles-over-amorphous-microscale-solid-dispersion-in-solubility-enhancement-of-poorly-soluble-drugs
#16
Li Ming Lim, The-Thien Tran, Wean Sin Cheow, Kunn Hadinoto
The solubility enhancement afforded by amorphous drug nanoparticles was demonstrated in several studies to be superior to the traditional amorphization approach by microscale amorphous solid dispersion (or micro ASD in short). A closer look at these studies, however, revealed that they were performed using a very limited number of poorly-soluble drug models (i.e. itraconazole and cefuroxime). Herein we aimed to re-examine the solubility enhancement and physical stability of amorphous nanoparticles relative to that of the micro ASD using a different poorly-soluble drug model, i...
September 6, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28884072/ochroconis-gallopava-bronchitis-mimicking-haemoptysis-in-a-patient-with-bronchiectasis
#17
M Bernasconi, C Voinea, P M Hauser, L P Nicod, R Lazor
Ochroconis gallopava is an anamorphic mould characterized by slow growth rate and production of a maroon pigment, which has been isolated worldwide from soil, thermal springs, decaying vegetation, and chicken litter. It has been reported to cause localized, mostly pulmonary, and systemic infection in severely immunocompromised patients. We describe the case of a 76-year-old woman known for ulcerative colitis-related bronchiectasis treated with low dose oral steroids, who developed a fungal bronchitis with dark, bloody-like, sputum which was initially misinterpreted as haemoptysis...
2017: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/28876392/antifungal-and-antioxidant-activity-of-fatty-acid-methyl-esters-from-vegetable-oils
#18
Maria E A Pinto, Sthéfane G Araújo, Marcela I Morais, Nívea P Sá, Caroline M Lima, Carlos A Rosa, Ezequias P Siqueira, Susana Johann, Luciana A R S Lima
Fatty acid methyl esters (FAMEs) were obtained from vegetable oils of soybean, corn and sunflower. The current study was focused on evaluating the antifungal activity of FAMEs mainly against Paracoccidioides spp., as well as testing the interaction of these compounds with commercial antifungal drugs and also their antioxidant potential. FAMEs presented small IC50 values (1.86-9.42 μg/mL). All three FAMEs tested showed antifungal activity against isolates of Paracoccidioides spp. with MIC values ranging from 15...
August 31, 2017: Anais da Academia Brasileira de Ciências
https://www.readbyqxmd.com/read/28872706/candida-bloodstream-infections-in-serbia-first-multi-center-report-of-a-national-prospective-observational-survey-in-intensive-care-units
#19
Valentina Arsić Arsenijević, Suzana Otašević, Dragana Janić, Predrag Minić, Jovan Matijašević, Deana Medić, Ivanka Savić, Snežana Delić, Suzana Laban Nestorović, Zorica Vasiljević, Mirjana Hadnadjev
Candida bloodstream infections (BSI) are a significant cause of mortality in intensive care units (ICU), hereof the prospective twelve-months (2014-2015) hospital and laboratory-based survey was performed at the Serbian National Reference Medical Mycology Laboratory (NRMML). Candida identification was done by a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and a susceptibility test, according to the Clinical and Laboratory Standards Institute methodology. Among 9 centers (265 beds; 10...
September 5, 2017: Mycoses
https://www.readbyqxmd.com/read/28872678/characterization-and-pharmacokinetic-study-of-itraconazole-solid-dispersions-prepared-by-solvent-controlled-precipitation-and-spray-dry-methods
#20
Taehoon Sim, Chaemin Lim, Jun Won Lee, Dong Wuk Kim, Youngsam Kim, Minsoo Kim, Seungmok Choi, Han-Gon Choi, Eun Seong Lee, Kil-Soo Kim, Wonku Kang, Kyung Taek Oh
OBJECTIVES: Solid dispersion formulations have attracted attention to improve solubility and bioavailability of water-insoluble drugs. In this study, the variation of solubility and bioavailability by different preparation methods were studied using itraconazole (ITZ) solid dispersions. METHODS: Itraconazole solid dispersions were prepared by a solvent-controlled precipitation method (SCPM) using HPMCAS-LF, HCl antisolvent or a spray-drying method (SDM) for comparison...
September 5, 2017: Journal of Pharmacy and Pharmacology
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