[PK/PD modeling of aminoglycoside nephrotoxicity]

Pathol Biol (Paris). 2003 Jun;51(4):234-6. doi: 10.1016/s0369-8114(03)00032-4.
[Article in French]

Abstract

Aminoglycosides are bactericidial antibiotics with a serum concentration-dependent activity. They are mainly eliminated by the kidneys and the main difficulty arising in clinical use is their uptake by the renal cortex which leads to nephrotoxicity. An ototoxicity is also reported. We propose a PK/PD modelling of aminoglycoside nephrotoxicity which unifies more fourty years of physiological knowledge. This deterministic model successively describes the pharmacokinetics of aminoglycosides, their storage into renal cortex, their effect on renal cells, their consequences on the renal function through tubuloglomerular feedback and the changes in the serum concentrations of creatinine that is considered as a toxicity marker. The simulation of the model displays the leading effect of the shape and daily-time of administration schedule on the search for minimizing toxicity.

Publication types

  • English Abstract

MeSH terms

  • Amikacin / adverse effects*
  • Amikacin / pharmacokinetics
  • Amikacin / pharmacology
  • Amikacin / therapeutic use
  • Anti-Bacterial Agents / adverse effects*
  • Anti-Bacterial Agents / pharmacokinetics
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Biomarkers
  • Chronotherapy
  • Creatinine / blood
  • Endocarditis, Bacterial / drug therapy
  • Feedback, Physiological
  • Glomerular Filtration Rate
  • Humans
  • Kidney Cortex / drug effects
  • Kidney Cortex / metabolism
  • Kidney Diseases / blood
  • Kidney Diseases / chemically induced*
  • Kidney Tubules / drug effects
  • Kidney Tubules / metabolism
  • Models, Biological*

Substances

  • Anti-Bacterial Agents
  • Biomarkers
  • Amikacin
  • Creatinine