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https://www.readbyqxmd.com/read/28214276/-in-vitro-antifungal-activity-of-azoles-and-amphotericin-b-against-malassezia-furfur-by-the-clsi-m27-a3-microdilution-and-etest-%C3%A2-methods
#1
Juan Camilo Galvis-Marín, María Ximena Rodríguez-Bocanegra, Adriana Del Pilar Pulido-Villamarín, Rubiela Castañeda-Salazar, Adriana Marcela Celis-Ramírez, Melva Yomary Linares-Linares
BACKGROUND: Malassezia furfur is a human skin commensal yeast that can cause skin and opportunistic systemic infections. Given its lipid dependant status, the reference methods established by the Clinical and Laboratory Standards Institute (CLSI) to evaluate antifungal susceptibility in yeasts are not applicable. AIMS: To evaluate the in vitro susceptibility of M. furfur isolates from infections in humans to antifungals of clinical use. METHODS: The susceptibility profile to amphotericin B, itraconazole, ketoconazole and voriconazole of 20 isolates of M...
February 14, 2017: Revista Iberoamericana de Micología
https://www.readbyqxmd.com/read/28198097/inibitory-effects-of-linalool-on-fungal-pathogenicity-of-clinical-isolates-of-microsporum-canis-and-microsporum-gypseum
#2
Kaltz V S Silva, Maria I O Lima, Gustavo N Cardoso, Aldeir S Santos, Gezaíldo S Silva, Fillipe O Pereira
In humans worldwide, Microsporum sp. is a frequent agent of dermatophytsosis. When considering the emergence of resistant fungi and the clinical relevance of dermatophytosis, terpene antifungal activity is of great interest. Linalool is a monoterpene alcohol with pharmacological properties. In this study, antifungal in vitro activity of linalool and ketoconazole (as a positive control) were evaluated against clinical isolates of M. canis and M. gypseum. The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of each drug were determined by broth microdilution...
February 15, 2017: Mycoses
https://www.readbyqxmd.com/read/28185218/clinical-pharmacokinetics-and-pharmacodynamics-of-pazopanib-towards-optimized-dosing
#3
REVIEW
Remy B Verheijen, Jos H Beijnen, Jan H M Schellens, Alwin D R Huitema, Neeltje Steeghs
Pazopanib is an inhibitor of the vascular endothelial growth factor receptor, platelet-derived growth factor receptor, fibroblast growth factor receptor and stem cell receptor c-Kit, and has been approved for the treatment of renal cell carcinoma and soft tissue sarcoma. The pharmacokinetics of pazopanib are complex and are characterized by pH-dependent solubility, large interpatient variability and low, non-linear and time-dependent bioavailability. Exposure to pazopanib is increased by both food and coadministration of ketoconazole, but drastically reduced by proton pump inhibitors...
February 10, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28185143/characterization-of-1-aminobenzotriazole-and-ketoconazole-as-novel-inhibitors-of-monoamine-oxidase-mao-an-in-vitro-investigation
#4
Abdul Naveed Shaik, Barbara W LeDuc, Ansar A Khan
BACKGROUND AND OBJECTIVES: 1-Aminobenzotriazole, a known time-dependent inhibitor of cytochrome P450 (CYP) enzymes, and ketoconazole, a strong inhibitor of the human CYP3A4 isozyme, are used as standard probe inhibitors to characterize the CYP and/or non-CYP-mediated metabolism of xenobiotics. In the present investigation, 1-Aminobenzotriazole and ketoconazole are characterized as potent monoamine oxidase (MAO) inhibitors in vitro using mouse, rat and human liver microsomes and S9 fractions...
February 9, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28179900/production-of-potent-antimicrobial-compounds-from-streptomyces-cyaneofuscatus-associated-with-fresh-water-sediment
#5
Zothanpuia, Ajit K Passari, Preeti Chandra, Vincent V Leo, Vineet K Mishra, Brijesh Kumar, Bhim P Singh
The genus Streptomyces under phylum actinobacteria has been recognized as a prolific source for the production of bioactive secondary metabolites. An actinobacterial strain designated as DST103 isolated from a wetland fresh water sediment of Tamdil Lake, Mizoram, Northeast, India was identified as Streptomyces cyaneofuscatus (KY287599) using 16SrRNA gene sequencing which shares 99.87% sequence similarity with Streptomyces cyaneofuscatus NRRL B-2570 (T) . The strain showed broad spectrum antimicrobial activities against Gram negative bacteria (Escherichia coli MTCC 739 and Pseudomonas aeruginosa MTCC 2453), Gram positive bacteria (Micrococcus luteus NCIM 2170 and Staphylococcus aureus MTCC 96) and yeast pathogen Candida albicans MTCC 3017)...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28170483/diagnosis-and-treatment-of-pituitary-adenomas-a-review
#6
Mark E Molitch
Importance: Pituitary adenomas may hypersecrete hormones or cause mass effects. Therefore, early diagnosis and treatment are important. Observations: Prevalence of pituitary adenomas ranges from 1 in 865 adults to 1 in 2688 adults. Approximately 50% are microadenomas (<10 mm); the remainder are macroadenomas (≥10 mm). Mass effects cause headache, hypopituitarism, and visual field defects. Treatments include transsphenoidal surgery, medical therapies, and radiotherapy...
February 7, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28167538/application-of-physiologically-based-pharmacokinetic-modeling-to-understanding-of-bosutinib-pharmacokinetics-prediction-of-drug-drug-and-drug-disease-interactions
#7
Chiho Ono, Poe-Hirr Hsyu, Richat Abbas, Cho-Ming Loi, Shinji Yamazaki
Bosutinib (Bosulif®) is an orally available Src/Abl tyrosine kinase inhibitor indicated for the treatment of patients with Ph+ chronic myelogenous leukemia. Bosutinib is predominantly metabolized by CYP3A4 as the primary clearance mechanism. The main objectives of the present study were to: 1) develop physiologically-based pharmacokinetic (PBPK) models of bosutinib, 2) verify and refine the PBPK models based upon clinical study results of bosutinib single-dose drug-drug interaction (DDI) with ketoconazole and rifampin, and single-dose drug-disease interaction (DDZI) in patients with renal and hepatic impairment, 3) apply the PBPK models to predict DDI outcome in patients with weak and moderate CYP3A inhibitors, and 4) apply the PBPK models to predict DDZI outcomes in renally and hepatically impaired patients after multiple-dose administration...
February 6, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28165809/ocular-ketoconazole-loaded-proniosomal-gels-formulation-ex-vivo-corneal-permeation-and-in-vivo-studies
#8
Ghada A Abdelbary, Maha M Amin, Mohamed Y Zakaria
CONTEXT: Vesicular drug carriers for ocular delivery have gained a real potential. Proniosomal gels as ocular drug carriers have been proven to be an effective way to improve bioavailability and patient compliance. OBJECTIVE: Formulation and in vitro/ex vivo/in vivo characterization of ketoconazole (KET)-loaded proniosomal gels for the treatment of ocular keratitis. MATERIALS AND METHODS: The effect of formulation variables; HLB value, type and concentration of non-ionic surfactants (Tweens, Spans, Brijs and Pluronics) with or without lecithin on the entrapment efficiency (EE%), vesicle size and in vitro KET release was evaluated...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28152378/synergism-between-macrolide-antibiotics-and-the-azole-fungicide-ketoconazole-in-growth-inhibition-testing-of-the-green-alga-pseudokirchneriella-subcapitata
#9
Takahiro Yamagishi, Yoshifumi Horie, Norihisa Tatarazako
Macrolide antibiotics and azole fungicides are detected widely in the aquatic environment as a result of their increased use in humans and animal livestock disease and their incomplete removal by wastewater treatment plants. In most cases, ecotoxicological tests are performed by using individual chemical substances, but because of the coexistence of a number of chemicals in the environment, organisms are exposed to many chemicals simultaneously. Therefore, it is important to evaluate effects of chemical interactions, adding to potential hazards of individual chemical...
January 16, 2017: Chemosphere
https://www.readbyqxmd.com/read/28139372/in%C3%A2-vitro-ocular-metabolism-and-bioactivation-of-ketoconazole-in-rat-rabbit-and-human
#10
Amanda L Cirello, Jennifer L Dumouchel, Mithat Gunduz, Christine E Dunne, Upendra A Argikar
Oral ketoconazole is clinically administered for treatment of severe cases for fungal keratitis. Pharmacodynamics and efficacy of oral and topical (ocular) ketoconazole have been explored in rabbit. However, metabolism of ketoconazole in the eye in any species is not well explored in any preclinical species or human. An understanding of ocular drug metabolism in the eye is crucial for ocular therapeutics to facilitate the risk assessment and development of potential drug candidates for the clinic. We aimed to investigate the metabolism of ketoconazole in rat, rabbit and human ocular S9 fractions...
November 19, 2016: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28133872/comparison-of-two-in%C3%A2-vitro-antifungal-sensitivity-tests-and-monitoring-during-therapy-of-sporothrix-schenckii-sensu-stricto-in-malaysian-cats
#11
Hock Siew Han, Rui Kano, Charles Chen, Chiara Noli
BACKGROUND: Feline sporotrichosis is common in Malaysia. Thermosensitivity and effects of azole treatment on fungal susceptibility are unknown. OBJECTIVES: To evaluate thermotolerance and antifungal susceptibility of feline Malaysian Sporothrix isolates, compare microdilution (MD) and E-test results, and investigate changes in susceptibility during azole therapy. METHODS: Sporothrix schenckii sensu stricto was isolated from 44 cats. Thermotolerance was determined via culture at 37°C for 7 days...
February 2017: Veterinary Dermatology
https://www.readbyqxmd.com/read/28128722/population-pharmacokinetics-of-ospemifene-and-safety-evaluation-of-pharmacokinetic-alterations-caused-by-intrinsic-and-extrinsic-factors%C3%A2
#12
Ryuji Kubota, Sayaka Matsumoto, Toshihiro Wajima
PURPOSE: To develop a population pharmacokinetic (PPK) model to assess factors influencing ospemifene pharmacokinetics and to assess safety for pharmacokinetic alteration observed in drug development. METHOD: A PPK model was constructed using pooled ospemifene concentrations. Covariates considered before start of the analysis were: age, race, body weight, BMI, albumin, alanine amino-transferase, bilirubin, and creatinine clearance. The expected distribution of ospemifene concentration was derived for the 4 cases in phase-1 studies that increased ospemifene exposure: administration to severe renal impairment subjects (case 1), administration to moderate hepatic impairment subjects (case 2), coadministration with ketoconazole (case 3), or coadministration with fluconazole (case 4)...
January 26, 2017: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28122787/a-physiologically-based-pharmacokinetic-modeling-approach-to-predict-drug-drug-interactions-of-sonidegib-lde225-with-perpetrators-of-cyp3a-in-cancer-patients
#13
Heidi J Einolf, Jocelyn Zhou, Christina Won, Lai Wang, Sam Rebello
Sonidegib (Odomzo®) is an orally available Smoothened inhibitor for the treatment of advanced basal cell carcinoma. Sonidegib was found to be metabolized primarily by cytochrome P450 (CYP)3A in vitro The effect of multiple doses of the strong CYP3A perpetrators, ketoconazole (KTZ) and rifampin (RIF), on sonidegib pharmacokinetics (PK) after a single 800 mg dose in healthy subjects was therefore assessed. This data was used to verify a physiologically-based pharmacokinetic (PBPK) model developed to: 1) bridge the clinical drug-drug interaction (DDI) study of sonidegib with KTZ and RIF in healthy subjects to the marketed dose (200 mg) in patients, 2) predict acute (14 days) versus long-term dosing of the perpetrators with sonidegib at steady-state, and 3) predict the effect of moderate CYP3A perpetrators on sonidegib exposure in patients...
January 25, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28120523/prioritisation-of-pharmaceuticals-based-on-risks-to-aquatic-environments-in-kazakhstan
#14
Bakhyt Aubakirova, Raikhan Beisenova, Alistair B A Boxall
Over the last 20 years, there has been increasing interest in the occurrence, fate, effects and risk of pharmaceuticals in the natural environment. However, we still have only limited or no data on ecotoxicological risks of many of the active pharmaceutical ingredients (APIs) currently in use. This is partly due to the fact that the environmental assessment of an API is an expensive, time-consuming and complicated process. Prioritisation methodologies, that aim to identify APIs of most concern in a particular situation, could therefore be invaluable in focusing experimental work on APIs that really matter...
January 25, 2017: Integrated Environmental Assessment and Management
https://www.readbyqxmd.com/read/28119491/reactive-oxygen-species-mediated-synergism-of-fenretinide-and-romidepsin-in-preclinical-models-of-t-cell-lymphoid-malignancies
#15
Monish R Makena, Balakrishna Koneru, Thinh H Nguyen, Min H Kang, C Patrick Reynolds
T-cell lymphoid malignancies (TCLMs) are in need of novel and more effective therapies. The histone deacetylase (HDAC) inhibitor romidepsin and the synthetic cytotoxic retinoid fenretinide both have achieved durable clinical responses in T-cell lymphomas as single agents. We investigated the potential for using these two agents in combination in TCLMs. We demonstrated cytotoxic synergy between romidepsin and fenretinide in fifteen TCLM cell lines at clinically-achievable concentrations that lacked cytotoxicity for non-malignant cells (fibroblasts and blood mononuclear cells)...
January 23, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28117738/in-vitro-biotransformation-of-two-human-cyp3a-probe-substrates-and-their-inhibition-during-early-zebrafish-development
#16
Evy Verbueken, Derek Alsop, Moayad A Saad, Casper Pype, Els M Van Peer, Christophe R Casteleyn, Chris J Van Ginneken, Joanna Wilson, Steven J Van Cruchten
At present, the zebrafish embryo is increasingly used as an alternative animal model to screen for developmental toxicity after exposure to xenobiotics. Since zebrafish embryos depend on their own drug-metabolizing capacity, knowledge of their intrinsic biotransformation is pivotal in order to correctly interpret the outcome of teratogenicity assays. Therefore, the aim of this in vitro study was to assess the activity of cytochrome P450 (CYP)-a group of drug-metabolizing enzymes-in microsomes from whole zebrafish embryos (ZEM) of 5, 24, 48, 72, 96 and 120 h post-fertilization (hpf) by means of a mammalian CYP substrate, i...
January 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28111792/inhibition-of-propionibacterium-acnes-lipase-activity-by-the-antifungal-agent-ketoconazole
#17
Mizuki Unno, Otomi Cho, Takashi Sugita
The common skin disease acne vulgaris is caused by Propionibacterium acnes. A lipase secreted by this microorganism metabolizes sebum and the resulting metabolites evoke inflammation in human skin. The antifungal drug ketoconazole inhibits P. acnes lipase activity. We previously showed that the drug also inhibits the growth of P. acnes. Thus, ketoconazole may serve as an alternative treatment for acne vulgaris, which is important because the number of antibiotic-resistant P. acnes strains has been increasing...
January 23, 2017: Microbiology and Immunology
https://www.readbyqxmd.com/read/28107620/chemical-interaction-of-protein-cysteine-residues-with-reactive-metabolites-of-methyleugenol
#18
Yukun Feng, Hui Wang, Qian Wang, Wenlin Huang, Ying Peng, Jiang Zheng
Methyleugenol (ME), an alkenylbenzene compound, is a natural ingredient of several herbs and is used as flavoring agent in foodstuffs and fragrance in cosmetics. The hepatotoxicity, cytotoxicity, and carcinogenesis of ME have been well documented, and metabolic activation has been suggested to involve in ME-induced toxicities. The objective of this study was to identify chemical identity of interactions of protein with reactive metabolites of ME. Modification of cysteine residues of protein was observed in microsomal incubations and mice after exposure to ME...
February 20, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28092844/enhanced-effect-in-combination-of-curcumin-and-ketoconazole-loaded-methoxy-poly-ethylene-glycol-poly-%C3%AE%C2%B5-caprolactone-micelles
#19
Fangfang Teng, Peizong Deng, Zhimei Song, Feilong Zhou, Runliang Feng
In order to enhance water-solubility and realize controlled release while keeping synergistic effects of ketoconazole and curcumin, drug-loaded methoxy poly (ethylene glycol)-b-poly (ε-caprolactone) micelles were prepared through thin membrane hydration method. Transmission electric microscopy and dynamitic light scattering characterization revealed the formation of ketoconazole- and curcumin-loaded micelles with an average size of 44.70nm and 39.56nm, respectively. The drug-loaded micelles endowed the two drugs' slow controlled release with water-solubility enhanced to 85 and 82000 folds higher than the corresponding raw drugs, respectively...
January 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28079539/preoperative-ketoconazole-therapy-for-primary-bilateral-adrenocorticotropic-hormone-independent-macronodular-adrenal-hyperplasia-syndrome
#20
Rukma Parthvi, Sunil Mehra
No abstract text is available yet for this article.
January 5, 2017: American Journal of Therapeutics
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