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https://www.readbyqxmd.com/read/29782822/simultaneous-determination-of-intestinal-permeability-and-potential-drug-interactions-of-complex-mixtures-using-caco-2-cells-and-high-resolution-mass-spectrometry-studies-with-rauwolfia-serpentina-extract
#1
Thomas J Flynn, Sanah N Vohra
Caco-2 cells are a commonly used model for estimating the intestinal bioavailability of single chemical entity pharmaceuticals. Caco-2 cells, when induced with calcitriol, also express other biological functions such as phase I (CYP) and phase II (glucuronosyltransferases) drug metabolizing enzymes which are relevant to drug-supplement interactions. Intestinal bioavailability is an important factor in the overall safety assessment of products consumed orally. Foods, including herbal dietary supplements, are complex substances with multiple chemical components...
May 18, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29770723/the-impact-of-azole-antifungal-drugs-on-imatinib-metabolism-in-human-liver-microsomes
#2
Xingxian Luo, Taifeng Li, Ze Yu, Xuecai Xue, Haiyang Zhao, Na Li, Liping Ma, Changqing Yang, Lin Huanglin, Wangyu Feng
1. Imatinib is widely used for the treatment of hematologic malignancies. It is common that imatinib is clinically co-prescribed with azole antifungal agents since these patients are more prone to invasive antifungal infection. The present study was to investigate the effects of azole antifungal drugs, including ketoconazole, fluconazole, voriconazole, itraconazole and posaconazole on imatinib metabolism. 2. The main metabolites, 1-OH midazolam and N-desmethyl imatinib, were determined in the absence and in the presence of various levels of ketoconazole, fluconazole, voriconazole, itraconazole and posaconazole...
May 17, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29766657/drug-drug-interaction-and-doping-effect-of-non-prohibited-drugs-on-the-urinary-excretion-profile-of-methandienone
#3
Monica Mazzarino, Franziska L Khevenhüller-Metsch, Ilaria Fiacco, Maria Kristina Parr, Xavier de la Torre, Francesco Botrè
The potential consequences of drug-drug interactions on the excretion profile of the anabolic androgenic steroid methandienone (17β-hydroxy-17α-methylandrosta-1,4-dien-3-one) are discussed here. More specifically, we have evaluated by in vitro and in vivo experiments the effects of seven non-prohibited drugs (fluconazole, ketoconazole, itraconazole, miconazole, fluoxetine, paroxetine and nefazodone) on the main metabolic pathways of methandienone. These are selected among those most commonly used by the athletes...
May 15, 2018: Drug Testing and Analysis
https://www.readbyqxmd.com/read/29761326/fusariosis-in-a-captive-south-american-sea-lion-otaria-flavescens-a-case-report
#4
Laura Reisfeld, Carlos Sacristán, Paloma Canedo, Bruna Schwarz, Ana Carolina Ewbank, Fernando Esperón, José Luiz Catão-Dias
Superficial mycoses are commonly reported in captive pinnipeds, usually maintained in wet and warm environments, favorable to fungal growth. Most superficial mycoses in pinnipeds have been described as difficult to treat; however, the majority of the reports come from past decades. Cutaneous lesions associated with opportunistic Fusarium sp. infections have been previously recognized in this taxon. We described the clinical signs, associated lesions and diagnosis (thermography, imprint cytology, histopathology, culture, electron microscopy, PCR) of a fusariosis case by Fusarium sp...
May 14, 2018: Mycopathologia
https://www.readbyqxmd.com/read/29749631/persistence-of-a-posaconazole-mediated-drug-drug-interaction-with-ranolazine-after-cessation-of-posaconazole-administration-impact-of-obesity-and-implications-for-patient-safety
#5
Christina R Chow, Jerold S Harmatz, Michael J Ryan, David J Greenblatt
The antianginal agent ranolazine (Ranexa®) is metabolized primarily by cytochrome P450-3A (CYP3A) enzymes. Coadministration with strong CYP3A inhibitors, such as ketoconazole and posaconazole, is contraindicated due to risk of QT prolongation from high levels of ranolazine. This study evaluated the time course of recovery from the posaconazole drug interaction in normal-weight and otherwise healthy obese subjects. Subjects received single doses of ranolazine in the baseline control condition, again during coadministration of posaconazole, and at 4 additional time points during the 2 weeks after posaconazole discontinuation...
May 11, 2018: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29744071/etomidate-in-the-control-of-severe-cushing-s-syndrome-by-neuroendocrine-carcinoma
#6
Alfredo Adolfo Reza-Albarrán, Gerson Geovany Andino Ríos, Laura Gabriela Gómez Herrera
Etomidate is a very effective drug in severe Cushing's syndrome that is refractory to ketoconazol. Control of the serum cortisol levels in ectopic Cushing's syndrome can be obtained with infusion rates much lower than those used in anesthesia, without respiratory side effects.
May 2018: Clinical Case Reports
https://www.readbyqxmd.com/read/29742964/efficient-generation-of-cynomolgus-monkey-induced-pluripotent-stem-cell-derived-intestinal-organoids-with-pharmacokinetic-functions
#7
Daichi Onozato, Misaki Yamashita, Ryosuke Fukuyama, Takumi Akagawa, Yuriko Kida, Akiko Koeda, Tadahiro Hashita, Takahiro Iwao, Tamihide Matsunaga
In preclinical studies, the cynomolgus monkey (CM) model is frequently used to predict the pharmacokinetics of drugs in the human small intestine, because of its evolutionary closeness to humans. Intestinal organoids that mimic the intestinal tissue have attracted attention in regenerative medicine and drug development. In this study, we generated intestinal organoids from CM induced pluripotent stem (CMiPS) cells and analysed their pharmacokinetic functions. CMiPS cells were induced into the hindgut; then, the cells were seeded on microfabricated culture vessel plates to form spheroids...
May 10, 2018: Stem Cells and Development
https://www.readbyqxmd.com/read/29739809/application-of-physiologically-based-pharmacokinetic-modeling-in-understanding-bosutinib-drug-drug-interactions-importance-of-intestinal-p-glycoprotein
#8
Shinji Yamazaki, Cho-Ming Loi, Emi Kimoto, Chester Costales, Manthena V Varma
Bosutinib is an orally available Src/Abl tyrosine kinase inhibitor indicated for the treatment of patients with Ph+ chronic myelogenous leukemia at a clinically recommended dose of 500 mg once daily. Clinical results indicated that increases in bosutinib oral exposures were supra-proportional at the lower doses (50 to 200 mg) and approximately dose-proportional at the higher doses (200 to 600 mg). Bosutinib is a substrate of CYP3A4 and P-glycoprotein and exhibits pH-dependent solubility with moderate intestinal permeability...
May 8, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29733808/investigation-of-anti-leishmanial-efficacy-of-miltefosine-and-ketoconazole-loaded-on-nanoniosomes
#9
R Nazari-Vanani, R Dehdari Vais, F Sharifi, N Sattarahmady, K Karimian, M H Motazedian, H Heli
Leishmaniasis is a group of parasitic disease caused by protozoa of Leishmania genus. Leishmania major accounts for the cutaneous leishmaniasis (CL). The current treatments of this disease are expensive with high toxicity and are associated to difficulties of healing and parasite resistance. Miltefosine and ketoconazole have been found to be effective against CL. In this study, miltefosine- and ketoconazole-loaded nanoniosomes were prepared by the thin film-hydration method, and their anti-leishmanial effects against Leishmania major promastigotes and amastigotes were evaluated...
May 4, 2018: Acta Tropica
https://www.readbyqxmd.com/read/29729667/bioprospection-of-actinobacteria-derived-from-freshwater-sediments-for-their-potential-to-produce-antimicrobial-compounds
#10
Zothanpuia, Ajit Kumar Passari, Vincent Vineeth Leo, Preeti Chandra, Brijesh Kumar, Chandra Nayak, Abeer Hashem, Elsayed Fathi Abd Allah, Abdulaziz A Alqarawi, Bhim Pratap Singh
BACKGROUND: Actinobacteria from freshwater habitats have been explored less than from other habitats in the search for compounds of pharmaceutical value. This study highlighted the abundance of actinobacteria from freshwater sediments of two rivers and one lake, and the isolates were studied for their ability to produce antimicrobial bioactive compounds. RESULTS: 16S rRNA gene sequencing led to the identification of 84 actinobacterial isolates separated into a common genus (Streptomyces) and eight rare genera (Nocardiopsis, Saccharopolyspora, Rhodococcus, Prauserella, Amycolatopsis, Promicromonospora, Kocuria and Micrococcus)...
May 5, 2018: Microbial Cell Factories
https://www.readbyqxmd.com/read/29724290/determination-of-the-contamination-by-azole-antimycotics-in-hospital-and-house-sewage-a-pilot-project-for-the-city-of-dresden
#11
H Knoth, S Ihme, R Oertel, A Matthes, C Ritter
Medicininal compounds and their metabolites are known to end up in sewerage and may slip through the cleaning process. Azole antimycotics are frequently used in hospitals, in particular for patients with cancer or immunosuppression. The aim of the study was to determine whether measurable azole antimycotic concentrations were introducted in the sewarage drain of an acute care hospital with special interest in oncology and hematology and the extent of removal of antimycotics by the sewerage treatment plant. For this, the concentrations of three commonly used azole antimycotics were measured in the effluent of the sewerage drain at the University Hospital Dresden, as well as in the influent and effluent of the main sewerage treatment plant of the city...
May 1, 2018: Die Pharmazie
https://www.readbyqxmd.com/read/29723430/relationships-of-changes-in-pharmacokinetic-parameters-of-substrate-drugs-in-drug-drug-interactions-on-metabolizing-enzymes-and-transporters
#12
Shinji Yamazaki
A general objective of drug-drug interaction (DDI) studies is to determine whether potential interactions of new molecular entities with concomitantly administered other drugs exist and, if DDIs occur, whether dosage adjustments are required. A typical end point for DDI evaluations is the ratio of area under the plasma concentration-time curve (AUC) of substrate drugs (AUCR), whereas the ratios of maximal plasma concentration (Cmax ) and terminal half-life (t1/2 ) are also important to understand DDI mechanisms (Cmax R and t1/2 R, respectively)...
May 3, 2018: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29716849/enhanced-uv-protection-of-ketoconazole-using-hyptis-suaveolens-micro-emulsion
#13
Ruttiros Khonkarn, Ornanong S Kittipongpatana, Vilai Boasouna, Siriporn Okonogi
Ketoconazole is photolabile antifungal drug. Photochemical reactions may decrease its therapeutic effect or induce toxic compounds. The aim of this study was to prepare ketoconazole loaded microemulsion containing H. suaveolens oil with antifungal and antioxidant powers in order to obtain effective antifungal formulation. The release study, antifungal activity and photostability test, were then evaluated. The results showed that optimized Hyptis suaveolens microemulsion for ketoconazole loading was selected through construction of pseudo-ternary phase diagrams...
May 2018: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29706576/antifungal-activity-of-gallesia-integrifolia-fruit-essential-oil
#14
Keila Fernanda Raimundo, Wanessa de Campos Bortolucci, Jasmina Glamočlija, Marina Soković, José Eduardo Gonçalves, Giani Andrea Linde, Nelson Barros Colauto, Zilda Cristiani Gazim
Gallesia integrifolia (Phytolaccaceae) is native to Brazil and has a strong alliaceous odor. The objective of this study was to identify the chemical composition of G. integrifolia fruit essential oil and evaluate fungicidal activity against the main food-borne diseases and food spoilage fungi. The essential oil was extracted by hydrodistillation and identified by GC-MS. From 35 identified compounds, 68% belonged to the organosulfur class. The major compounds were dimethyl trisulfide (15.49%), 2,8-dithianonane (52...
April 12, 2018: Brazilian Journal of Microbiology: [publication of the Brazilian Society for Microbiology]
https://www.readbyqxmd.com/read/29695615/metabolism-of-a-5ht6-antagonist-2-methyl-1-phenylsulfonyl-4-piperazin-1-yl-1h-benzo-d-imidazole-sam-760-impact-of-sulfonamide-metabolism-on-diminution-of-a-ketoconazole-mediated-clinical-drug-drug-interaction
#15
Aarti Sawant-Basak, R Scott Obach, Angela C Doran, Peter Lockwood, Klaas Schildknegt, Hongying Gao, Jessica Mancuso, Susanna Tse, Tom Comery
SAM-760, (2-methyl-1-(phenylsulfonyl)-4-(piperazin-1-yl)-1H-benzo[d]imidazole), a 5HT6 antagonist, was investigated in humans for the treatment of Alzheimer's dementia. In liver microsomes and recombinant CYP450 isozymes, SAM-760 was predominantly metabolized by CYP3A (~85%). Based on these observations and an expectation of 5-fold magnitude of interaction with moderate to strong CYP3A inhibitors, a clinical DDI study was performed. In presence of ketoconazole, mean Cmax and AUC0-inf of SAM-760 showed only a modest increase by 30% and 38%, respectively...
April 25, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29694638/a-review-of-cushing-s-disease-treatment-by-the-department-of-neuroendocrinology-of-the-brazilian-society-of-endocrinology-and-metabolism
#16
Márcio Carlos Machado, Maria Candida Barisson Vilares Fragoso, Ayrton Custódio Moreira, César Luiz Boguszewski, Leonardo Vieira Neto, Luciana A Naves, Lucio Vilar, Luiz Antônio de Araújo, Nina Rosa Castro Musolino, Paulo Augusto C Miranda, Mauro A Czepielewski, Monica R Gadelha, Marcello Delano Bronstein, Antônio Ribeiro-Oliveira
The treatment objectives for a patient with Cushing's disease (CD) are remission of hypercortisolism, adequate management of co-morbidities, restoration of the hypothalamic-pituitary-adrenal axis, preservation of fertility and pituitary function, and improvement of visual defects in cases of macroadenomas with suprasellar extension. Transsphenoidal pituitary surgery is the main treatment option for the majority of cases, even in macroadenomas with low probability of remission. In cases of surgical failure, another subsequent pituitary surgery might be indicated in cases with persistent tumor imaging at post surgical magnetic resonance imaging (MRI) and/or pathology analysis of adrenocorticotropic hormone-positive (ACTH+) positive pituitary adenoma in the first procedure...
February 2018: Archives of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29692458/antimicrobial-susceptibility-of-tinea-capitis-in-children-from-egypt
#17
Reham William Doss, Abdel-Aziz El-Rifaie, Nagla Radi, Aya Yehia El-Sherif
Background: Dermatophytic fungi of genera Trichophyton and Microsporum are the most important fungal species causing tinea capitis. Choice of treatment for tinea capitis is determined by the species of fungus. Aim: The aim of the study was to investigate the most prevalent fungal species causing tinea capitis in children from Egypt and the most useful antifungal agent for treatment. Patients and Methods: A total of 100 patients diagnosed clinically with tinea capitis were included in the study...
March 2018: Indian Journal of Dermatology
https://www.readbyqxmd.com/read/29680774/targeting-hypothalamic-pituitary-adrenal-axis-hormones-and-sex-steroids-for-improving-cognition-in-major-mood-disorders-and-schizophrenia-a-systematic-review-and-narrative-synthesis
#18
REVIEW
Virginia Soria, Alexandre González-Rodríguez, Elena Huerta-Ramos, Judith Usall, Jesús Cobo, Miquel Bioque, Juan David Barbero, Clemente García-Rizo, Meritxell Tost, José Antonio Monreal, Javier Labad
Cognitive deficits are a core feature of serious mental illnesses such as schizophrenia, major depressive disorder (MDD) and bipolar disorder (BD) and are a common cause of functional disability. There is limited efficacy of pharmacological interventions for improving the cognitive deficits in these disorders. As pro-cognitive pharmacological treatments are lacking, hormones or drugs that target the endocrine system may become potential candidates for 'repurposing' trials aiming to improve cognition. We aimed to study whether treatment with drugs targeting the hypothalamic-pituitary-adrenal (HPA) axis and sex steroids can improve cognition in patients with schizophrenia, MDD or BD...
April 14, 2018: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/29674118/germline-variant-in-hsd3b1-1245-a-c-and-response-to-abiraterone-acetate-plus-prednisone-in-men-with-new-onset-metastatic-castration-resistant-prostate-cancer
#19
Andrew W Hahn, David M Gill, Roberto H Nussenzveig, Austin Poole, Jim Farnham, Lisa Cannon-Albright, Neeraj Agarwal
BACKGROUND: The HSD3B1 gene encodes the enzyme 3β-hydroxysteroid dehydrogenase-1 (3βHSD1), which catalyzes adrenal androgen precursors into dihydrotestosterone, the most potent androgen. Recently, the HSD3B1 (1245C) variant was shown to predict shorter duration of response to androgen deprivation therapy with medical or surgical castration in the setting of castration-sensitive prostate cancer (CSPC). The HSD3B1 (1245C) variant also predicts longer duration of response to ketoconazole in men with castration-resistant prostate cancer (CRPC)...
March 27, 2018: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29673770/the-in-vitro-efficacy-of-sunsmile-%C3%A2-fruit-vegetable-rinse-against-pathogenic-strains-of-prototheca-algae-that-cause-mastitis-in-cows
#20
B Grzesiak, H Krukowski, A Głowacka
The research concerns algae of the genus Prototheca. They are found in the natural environment and they can cause a disease in animals and humans called protothecosis. The aim of the study was to evaluate the in vitro activity of the fruit and vegetable rinse agent SunSmile® Fruit & Vegetable Rinse (Sunrider International) against P. zopfii isolates. The materials consisted of ten P. zopfii strains isolated from the milk of cows with mastitis. The following antifungal chemotherapeutic agents were also used in the study for comparison: nystatin, ketoconazole, amphothericin B, miconazole, clotrimazole, econazole, fluconazole, and flucytosine...
April 16, 2018: Journal de Mycologie Médicale
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