Model-informed drug development for antimicrobials: translational pharmacokinetic-pharmacodynamic modelling of apramycin to facilitate prediction of efficacious dose in complicated urinary tract infections
2024

Model-informed drug development for apramycin in urinary tract infections

Sample size: 80 publication Evidence: high

Author Information

Author(s): Hernández-Lozano Irene, Aranzana-Climent Vincent, Cao Sha, Matias Carina, Ulf Hansen Jon, Liepinsh Edgars, Hughes Diarmaid, Hobbie Sven N, Vingsbo Lundberg Carina, Friberg Lena E

Primary Institution: Uppsala University

Hypothesis

Can pharmacokinetic-pharmacodynamic modeling predict effective doses of apramycin for treating complicated urinary tract infections?

Conclusion

The study successfully developed a model that predicts an effective dose of apramycin for treating complicated urinary tract infections in humans.

Supporting Evidence

  • The PKPD model showed a significant reduction in bacterial load in kidneys and bladder tissue.
  • Simulations suggested that an 11 mg/kg daily dose would be sufficient to achieve bacterial stasis in humans.
  • The study integrated longitudinal in vivo data to enhance predictions of drug efficacy.

Takeaway

Researchers used a special model to figure out how much apramycin medicine people need to fight urinary infections. They found that a dose of about 11 mg/kg should work well.

Methodology

The study involved in vitro and in vivo experiments with E. coli strains and developed a pharmacokinetic-pharmacodynamic model to assess apramycin efficacy.

Limitations

The study required a significant number of animals to obtain longitudinal data, which may limit the generalizability of the findings.

Statistical Information

P-Value

p<0.05

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1093/jac/dkae409

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