Pharmacokinetic parameters explain the therapeutic activity of antimicrobial agents in a silkworm infection model

@article{Paudel2018PharmacokineticPE,
  title={Pharmacokinetic parameters explain the therapeutic activity of antimicrobial agents in a silkworm infection model},
  author={Atmika Paudel and Suresh Panthee and Makoto Urai and Hiroshi Hamamoto and Tomohiko Ohwada and Kazuhisa Sekimizu},
  journal={Scientific Reports},
  year={2018},
  volume={8}
}
Poor pharmacokinetic parameters are a major reason for the lack of therapeutic activity of some drug candidates. Determining the pharmacokinetic parameters of drug candidates at an early stage of development requires an inexpensive animal model with few associated ethical issues. In this study, we used the silkworm infection model to perform structure-activity relationship studies of an antimicrobial agent, GPI0039, a novel nitrofuran dichloro-benzyl ester, and successfully identified compound… Expand
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References

SHOWING 1-10 OF 38 REFERENCES
Advantages of the Silkworm As an Animal Model for Developing Novel Antimicrobial Agents
TLDR
It is proposed that the utilization of silkworm infection model will facilitate the discovery of novel therapeutically effective antimicrobial agents, and the silkworm antibiotic screening model is very effective for identifying novel antibiotics. Expand
A Novel Spiro-Heterocyclic Compound Identified by the Silkworm Infection Model Inhibits Transcription in Staphylococcus aureus
TLDR
It is revealed that GPI0363 could bind to SigA, inhibit promoter-specific transcription in vitro, and prolong the survival of mice infected with methicillin-resistant S. aureus infections. Expand
Galleria mellonella as a model system to test the pharmacokinetics and efficacy of antibiotics against Burkholderia pseudomallei.
TLDR
The hypothesis that G. mellonella can be used to screen antimicrobial efficacy in humans is supported, and the pharmacokinetic parameters of clinically relevant antibiotics in this model system are determined. Expand
Silkworm as a model animal to evaluate drug candidate toxicity and metabolism.
TLDR
Findings suggest that chemicals are metabolized through a pathway common to both mammals and silkworms: reaction with cytochrome P450, conjugation with hydroxylated compounds, and excretion. Expand
Discovery of a new antifungal agent ASP2397 using a silkworm model of Aspergillus fumigatus infection
TLDR
The novel antifungal compound ASP2397 was identified that not only cured infected silkworm larvae but also increased the rates of survival of mice infected with A. fumigatus. Expand
Lysocin E is a new antibiotic that targets menaquinone in the bacterial membrane.
TLDR
Lysocin E interacted with menaquinone in the bacterial membrane to achieve its potent bactericidal activity, a mode of action distinct from that of any other known antibiotic, indicating that lysOCin E comprises a new class of antibiotic. Expand
Evaluation of Galleria mellonella larvae for measuring the efficacy and pharmacokinetics of antibiotic therapies against Pseudomonas aeruginosa infection.
TLDR
Galleria mellonella larvae were sensitive to P. aeruginosa infection, and increasing inoculum doses of live cells resulted in greater larval mortality, and there was a clear correlation between measured antibiotic pharmacokinetics and the therapeutic effect. Expand
Quantitative Evaluation of the Therapeutic Effects of Antibiotics Using Silkworms Infected with Human Pathogenic Microorganisms
TLDR
The ineffectiveness of oral administration of vancomycin to silkworms is due to a lack of intestinal absorption, and chloramphenicol, which is effective by oral administration, appeared in the silkworm hemolymph soon after injection into the midgut, whereas vancomYcin did not. Expand
Pharmaceutical characterization of novel tenofovir liposomal formulations for enhanced oral drug delivery: in vitro pharmaceutics and Caco-2 permeability investigations
TLDR
An efficient reverse-phase high-performance liquid chromatography method was developed and validated and successfully applied to characterize both in vitro encapsulation efficiency and Caco-2 permeability transport for the pharmaceutical assessment of novel tenofovir formulations. Expand
Nosokomycins, new antibiotics discovered in an in vivo-mimic infection model using silkworm larvae. I: Fermentation, isolation and biological properties
TLDR
The in vivo-mimic assay system using silkworm larvae was used as a screening tool to discover antibiotics against methicillin-resistant Staphylococcus aureus and inhibited the growth of MRSA with MIC values of 0.125 μg ml−1 using the liquid microdilution method. Expand
...
1
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3
4
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