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Antifungal Agents01:15

Antifungal Agents

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Amphotericin B is a broad-spectrum antifungal agent that exploits structural differences between fungal and mammalian cell membranes. Its amphipathic structure—featuring a hydrophobic polyene-lactone ring and a hydrophilic region containing mycosamine and carboxylic acid groups—enables selective binding to ergosterol, a sterol predominantly found in fungal plasma membranes. This selective interaction underlies the drug’s antifungal activity, although weak binding to...
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PK–PD modeling has significantly influenced FDA regulatory decisions, particularly drug approval, dosage optimization, and labeling. These models integrate pharmacokinetics (PK) and pharmacodynamics (PD) to predict drug behavior and effects, aiding in optimizing dosing regimens and enhancing the probability of clinical trial success.One notable example is Nesiritide (Natrecor®), a recombinant human brain natriuretic peptide for treating acute decompensated congestive heart failure...
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Anthelmintic drugs differ significantly from antiparasitic therapies targeting protozoa, primarily due to differences in parasite biology. Whereas most protozoal treatments act on proliferating cells, anthelmintics are typically directed against mature, nonproliferative helminths. The therapeutic approach considers the helminth's reliance on neuromuscular coordination, glucose metabolism, and microtubular integrity for survival, reproduction, and localization within the host. Most anthelmintics...
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Modified-release dosage forms are designed to address the limitations of drugs with short biological half-lives. These forms maintain stable therapeutic drug concentrations over extended periods, reducing the need for frequent dosing. A consistent drug level helps minimize peak-trough fluctuations, which can reduce adverse effects, lower the risk of drug resistance, and improve overall treatment effectiveness.One common type of modified-release form is the extended-release (ER) formulation. ER...
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Intermittent intravenous (IV) infusion is a method of drug administration where medications are delivered over short infusion periods followed by intervals of no drug delivery. This approach helps to prevent sustained high drug concentrations in the bloodstream, reducing the risk of adverse effects associated with prolonged exposure. Unlike continuous infusion, steady-state concentrations may not be achieved during a single dosing cycle but can be reached through repeated...
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Whole Genome Sequencing of Candida glabrata for Detection of Markers of Antifungal Drug Resistance
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CD101: a novel long-acting echinocandin.

Yanan Zhao1, Winder B Perez1, Cristina Jiménez-Ortigosa1

  • 1Public Health Research Institute, Rutgers Biomedical and Health Sciences, New Jersey Medical School, Newark, NJ, USA.

Cellular Microbiology
|June 30, 2016
PubMed
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CD101 shows potent antifungal activity against Candida, including resistant strains. This novel echinocandin drug demonstrates comparable efficacy to micafungin and may prevent antifungal resistance.

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Area of Science:

  • Mycology
  • Pharmacology
  • Infectious Diseases

Background:

  • Invasive candidiasis poses a significant threat, necessitating new antifungal agents.
  • Echinocandin resistance in Candida species is an emerging clinical challenge.
  • CD101 is a novel echinocandin with potential against susceptible and resistant fungal infections.

Purpose of the Study:

  • To evaluate the antifungal properties of CD101 against various Candida strains.
  • To compare CD101's efficacy and resistance profile with micafungin.
  • To assess CD101's potential in treating and preventing echinandin resistance.

Main Methods:

  • Antifungal susceptibility testing on 95 Candida strains, including 30 caspofungin-resistant isolates.
  • Enzyme inhibition assays measuring glucan synthase activity.
  • In vivo efficacy studies in a murine model of invasive candidiasis.
  • Pharmacokinetic profiling in mice.

Main Results:

  • CD101 demonstrated comparable antifungal potency to micafungin against susceptible and resistant Candida strains.
  • Both CD101 and micafungin showed similar inhibition of glucan synthase and mutant prevention concentrations.
  • CD101 exhibited comparable or superior efficacy in a murine model of invasive candidiasis.
  • CD101 displayed an exceptional long-lived pharmacokinetic profile after a single dose.

Conclusions:

  • CD101 is a promising antifungal agent for invasive candidiasis.
  • CD101 maintains efficacy against echinocandin-resistant Candida strains.
  • CD101 has the potential to prevent the emergence of antifungal resistance.