Elution of metronidazole and gentamicin from polymethylmethacrylate beads

Vet Surg. 2003 May-Jun;32(3):251-61. doi: 10.1053/jvet.2003.50024.

Abstract

Objective: To characterize the elution and bioactivity of metronidazole and gentamicin sulfate polymerized, individually and in combination, with polymethylmethacrylate (PMMA).

Study design: In vitro experimental study.

Methods: PMMA beads containing metronidazole (3 concentrations), gentamicin sulfate, or metronidazole and gentamicin sulfate were immersed in 5 mL of phosphate-buffered saline in triplicate. Eluent was replaced at specified time intervals for 1 or 21 days, and antibiotic concentrations were measured by high-performance liquid chromatography. Changes in antibiotic bioactivity attributable to polymerization or copolymerization of the antibiotics with PMMA, ethylene oxide sterilization, and storage of AIPMMA beads containing metronidazole were evaluated.

Results: Antibiotic elution patterns were similar for all groups. Day 1 elution for groups containing metronidazole or gentamicin individually represented a mean 63%-66% and 79%, respectively, of the 21-day total. Approximately 50% of the day 1 elution occurred during the first hour. The elution of metronidazole was dose dependent. The elution of metronidazole (day 3-21) and gentamicin (all days) was significantly greater when metronidazole and gentamicin were combined (P <.05). The addition of metronidazole delayed polymerization of PMMA. Neither polymerization nor copolymerization of metronidazole and gentamicin with PMMA, gas sterilization, or 2-month storage of beads containing metronidazole significantly affected antimicrobial bioactivity.

Conclusions: Metronidazole elution from PMMA was dose dependent. Copolymerization of metronidazole and gentamicin sulfate in PMMA resulted in increased rates of elution. Intraoperative preparation of metronidazole-impregnated PMMA beads is not practical, but sterilization and storage for 2 months should not affect efficacy.

Clinical relevance: The local delivery of biologically active metronidazole and gentamicin by elution from PMMA is feasible.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / pharmacokinetics
  • Anti-Bacterial Agents / pharmacology*
  • Bacteroides fragilis / drug effects*
  • Bone Cements / chemistry
  • Bone Diseases, Infectious / prevention & control
  • Bone Diseases, Infectious / veterinary*
  • Delayed-Action Preparations
  • Drug Storage
  • Escherichia coli / drug effects*
  • Gentamicins / administration & dosage
  • Gentamicins / pharmacokinetics
  • Gentamicins / pharmacology*
  • Metronidazole / administration & dosage
  • Metronidazole / pharmacokinetics
  • Metronidazole / pharmacology*
  • Microbial Sensitivity Tests
  • Polymethyl Methacrylate / chemistry

Substances

  • Anti-Bacterial Agents
  • Bone Cements
  • Delayed-Action Preparations
  • Gentamicins
  • Metronidazole
  • Polymethyl Methacrylate