Systemic exposure to tobramycin after local antibiotic treatment with calcium sulphate as carrier material

Arch Orthop Trauma Surg. 2011 May;131(5):657-62. doi: 10.1007/s00402-010-1192-2. Epub 2010 Oct 12.

Abstract

Introduction: Osteoset(®) T is a calcium sulphate void filler containing 4% tobramycin sulphate, used to treat bone and soft tissue infections. Despite systemic exposure to the antibiotic, there are no pharmacokinetic studies in humans published so far. Based on the observations made in our patients, a model predicting tobramycin serum levels and evaluating their toxicity potential is presented.

Methods: Following implantation of Osteoset(®) T, tobramycin serum concentrations were monitored systematically. A pharmacokinetic analysis was performed using a non-linear mixed effects model based on a one compartment model with first-degree absorption.

Results: Data from 12 patients treated between October 2006 and March 2008 were analysed. Concentration profiles were consistent with the first-order slow release and single-compartment kinetics, whilst showing important variability. Predicted tobramycin serum concentrations depended clearly on both implanted drug amount and renal function.

Discussion and conclusion: Despite the popularity of aminoglycosides for local antibiotic therapy, pharmacokinetic data for this indication are scarce, and not available for calcium sulphate as carrier material. Systemic exposure to tobramycin after implantation of Osteoset(®) T appears reassuring regarding toxicity potential, except in case of markedly impaired renal function. We recommend in adapting the dosage to the estimated creatinine clearance rather than solely to the patient's weight.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / blood
  • Anti-Bacterial Agents / pharmacokinetics*
  • Bone Diseases, Infectious / drug therapy*
  • Calcium Sulfate / pharmacology
  • Female
  • Humans
  • Joint Diseases / drug therapy*
  • Male
  • Middle Aged
  • Soft Tissue Infections / drug therapy*
  • Tobramycin / administration & dosage
  • Tobramycin / blood
  • Tobramycin / pharmacokinetics*

Substances

  • Anti-Bacterial Agents
  • Tobramycin
  • Calcium Sulfate