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Pharmacokinetics of anti-infectious reagents in silkworms

Hiroshi Hamamoto1, Ryo Horie1, Kazuhisa Sekimizu2

  • 1Teikyo University Institute of Medical Mycology, 359 Otsuka, Hachioji, Tokyo, 192-0395, Japan.

Scientific Reports
|July 3, 2019
PubMed

Insights

Silkworms offer a viable model for studying antimicrobial agents, showing pharmacokinetic similarities to mammals. This insect model accurately reflects drug metabolism and therapeutic potential, aiding antimicrobial drug discovery.

Area of Science:

  • Pharmacology
  • Microbiology
  • Toxicology

Background:

  • Silkworm infection models are valuable for screening new antimicrobial drugs.
  • Cytochrome P450 enzymes are crucial for metabolizing antimicrobial agents.

Purpose of the Study:

  • To investigate the pharmacokinetics and metabolism of antimicrobial agents using silkworms.
  • To assess the utility of silkworms as a model for predicting mammalian responses to antimicrobials.

Main Methods:

  • Determined pharmacokinetic parameters (half-life, distribution volume) from hemolymph concentrations.
  • Compared silkworm hemolymph protein binding with mammalian serum.
  • Localized cytochrome P450 enzyme activity in silkworm midgut.

Main Results:

  • Silkworm pharmacokinetic parameters mirrored those in mammalian models.
  • Antifungal agents with high protein binding in mammals showed similar behavior in silkworms.
  • Silkworm midgut demonstrated significant cytochrome P450 activity, metabolizing compounds similarly to humans.

Conclusions:

  • Silkworm pharmacokinetics of antimicrobial agents are fundamentally similar to mammals.
  • The silkworm infection model effectively predicts therapeutic effects based on pharmacokinetics.
  • Silkworms provide a relevant and efficient model for antimicrobial drug development.

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