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Ketoconazole - PubMed

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Last Updated: 13 April 2022

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Ketoconazole/calix[n]arenes-based compounds improve the antifungal activity against azole-resistant Candida isolates.

Candida spp-in vitro antifungal activity was found in vitro superior or similar to free KTZ against Candida spp. In addition, CX6Na/KTZ had no toxic effect on Galleria mellonella larvae, and infected larvae with C. albicans and C. auris were not harmful at a lower dose than free KTZ. CX6Na/KTZ may have a potential solution to mycosis, especially by advancing KTZ inhibitory activity against azole-resistant Candida.

Source link: https://doi.org/10.1016/j.mycmed.2022.101254


In vitro selection of ketoconazole-pentamidine-resistant Leishmania (Viannia) braziliensis strains.

The use of ketoconazole pentamidine as a new treatment approach for New World cutaneous leishmaniasis could be a promising treatment option for New World cutaneous leishmaniasis. Promastigotes resistant to KTZ or PMD were available three times earlier than the combined KTZ + PMD-resistant strains. Resistant parasites were three to ten times more susceptible to KTZ and PMD than WT parasites. After a KTZ + PMD-resistant parasite infection infection, similar parasite fitness according to our measured characteristics was found except for in vivo infection, in which a delay in the onset of cutaneous lesions was observed. CONCLUSION: Combined treatment of KTZ and PMD delayed the onset of parasite resistance in vitro and was more effective in vitro than either drug alone for WT and all resistant strains. Parasites resistant to KTZ and PMD were less virulent to mice and maintained their resistance phenotype on intracellular amastigotes, but not without drug pressure or after mouse infections.

Source link: https://doi.org/10.1016/j.exppara.2021.108206


A supramolecular thermosensitive gel of ketoconazole for ocular applications: In silico, in vitro, and ex vivo studies.

The incidence of corneal fungal infections remains a growing problem around the world. The optimized KTZ-SBE-CD system was developed in silico with docking and dynamics simulations, followed by wet-lab experiments. The supramolecular complex enhanced KTZ's solubility by 5-folds and led to a 10-fold increase in drug release compared to the pure KTZ. Theex vivocorneal permeation tests showed higher permeation from KTZ-SBE-CD in situ gel than KTZin situ gel. The physicochemical characteristics of KTZ were successfully improved by In silico's led construction of KTZ-SBE-CD inclusion complexes, which also improved the physicochemical characteristics of the region. In addition, the conversion of the KTZ-SBE-CD complex into an in situ gel greatly enhanced the precorneal retention and permeation of KTZ, indicating that the new formulation is a viable alternative to treating fungal keratitis.

Source link: https://doi.org/10.1016/j.ijpharm.2021.121409


Does the circulating ketoconazole metabolite N-deacetyl ketoconazole contribute to the drug-drug interaction potential of the parent compound?

N-deacetyl ketoconazole has been identified as the key ketoconazole metabolite, which is still unknown for humans and in rodents. We therefore investigated in vitro whether DAK also inhibits the human CYPs and drug transporters in human plasma from healthy volunteers after receiving a single oral dose of 400 mg ketoconazole. DAK levels in human plasma were only 3. 1 % of the parent compound after a single oral dose of 400 mg ketoconazole.

Source link: https://doi.org/10.1016/j.ejps.2021.106076


Arylacetamide deacetylase knockout mice are sensitive to ketoconazole-induced hepatotoxicity and adrenal insufficiency.

Orally administered ketoconazole will rarely cause liver disease and adrenal insufficiency. Using Aadac knockout mice, this research sought to determine the role of AADAC in ketoconazole-induced toxicity in vivo. In Aadac knockout mice, the metabolite of ketoconazole, and N-deacetylketoconazole, a hydrolyzed metabolite of ketoconazole, were significantly higher and lower than those in wild-type mice, respectively. Aadac knockout mice died faster than wild-type mice with higher plasma alanine transaminase and lower corticosterone levels, respectively, representing liver injury and steroidogenesis inhibition, respectively. ketoconazole-induced toxicities can be reduced by this in vivo research.

Source link: https://doi.org/10.1016/j.bcp.2021.114842


Permeabilized Cryopreserved Human Hepatocytes as an Exogenous Metabolic System in a Novel Metabolism-Dependent Cytotoxicity Assay for the Evaluation of Metabolic Activation and Detoxification of Drugs Associated with Drug-Induced Liver Injuries: Results with Acetaminophen, Amiodarone, Cyclophosphamide, Ketoconazole, Nefazodone, and Troglitazone.

Our results show that MDCA can be used to reveal metabolic activation and detoxification pathways, providing evidence that can be used in drug manufacturing to aid in drug design optimization to minimize toxicity reduction and aid in the identification of metabolic risk factors for drug toxicity. GSH detoxification, which is a significant feature of drugs with idiosyncratic hepatotoxicity, represents an endpoint for the identification of drugs that have cytotoxic reactive metabolites. SIGNIFICANCE STATEMENT: The use of the metabolism-dependent cytotoxicity assay for the elucidation of drug metabolism and detoxification pathways in drug toxicity may help to identify drug structure optimization in drug development in order to reduce hepatotoxic risk and aid in the determination of metabolism-based risk factors. The detoxification of glyphic hepatotoxicity by Glutathione detoxification marks a turning point for the identification of cytotoxic reactive metabolites in drugs that may be used in the analysis of idiosyncratic hepatotoxicity.

Source link: https://doi.org/10.1124/dmd.121.000645


Toxicokinetic and bioavailability studies on retrorsine in mice, and ketoconazole-induced alteration in toxicokinetic properties.

The aim of this research was to establish a high-performance liquid chromatography-tandem mass spectrometric system for serum RTS determination in mice. As mobile phases, serum samples were deproteinated by acetonitrile, isolated on a C18-PFP column, and delivered at 0. 8 ml/min with an eluting unit composed of water containing 0. 1% formic acid and acetonitrile containing 0. 1% formic acid. Both RTS and the internal standard S-hexylglutathione were quantitatively monitored, with precursor-to-product transitions of m/z 32. 1 246. 3, respectively. After intravenous, oral administration, and co-treated with ketoconazole, RTS showed a long half-life and good bioavailability in mice, a validated LC-MS/MS technique was used to analyze serum RTS in mice. The peak serum concentration and area under the concentration-time curve were higher when co-administration of ketoconazole, as well as decreasing the clearance and mean residence time.

Source link: https://doi.org/10.1002/bmc.5270


Real World Analysis of Response Rate and Efficacy of Oral Ketoconazole in Patients with Recalcitrant Tinea Corporis and Cruris.

In the treatment of recalcitrant tinea corporis and cruris, we wanted to determine the response rate, effectiveness, relapse rate, and side effects of oral ketoconazole. Patients with tinea cruris or corporis who had failed medical care with conventional antifungal drugs and treated with oral KZ were screened for patients with tinea cruris or corporis. Patients with tinea corporis/cruris who had received antifungal therapy before were recruited in the study. In 76. 7% patients, the KOH mount and culture were positive. With various antifungal susceptibility tests, Ketoconazole demonstrated the lowest minimum inhibitory concentration on antifungal susceptibility tests. Patients with less than 40% clearance at 2 weeks had a 68. 9% lower risk of being cured of disease. On therapy, two patients' liver enzymes increased. According to our report, KZ can be used as an alternative drug in situations where traditional antifungal treatments are ineffective.

Source link: https://doi.org/10.4269/ajtmh.21-0505


Ketoconazole resistant Candida albicans is sensitive to a wireless electroceutical wound care dressing.

Bacteria are killed by bacteria and the disruption of bacterial biofilm is disrupted by a wireless electroceutical dressing fabric. This study investigated whether the small electric field created by WED is able to combat infection caused by ketoconazole-resistant yeast Candida albicans, compared to the national level. Unlike ketoconazole, WED prevented yeast from hyphal transition and downregulated EAP1 cell attachment, reducing cell attachment by 80%. On NRG1, TUP1, and EFG1, Ketoconazole failed to reproduce the effects of WED on NRG1, TUP1, and EFG1. This work is the first evidence that poor electric field can be helpful in controlling pathogens that are otherwise unknown to be antibiotic resistant.

Source link: https://doi.org/10.1016/j.bioelechem.2021.107921

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions