Related Experiment Video
Updated: Jun 24, 2026
A Novel Method to Determine the Longitudinal Antibacterial Activity of Drug-Eluting Materials
Published on: March 3, 2023
Moxifloxacin Concentrations in the Knee Joint, Tibial Bone, and Soft Tissue When Combined with Rifampicin: A
Josefine Slater1,2,3, Maiken Stilling1,2,3, Pelle Hanberg1,2,3,4
1Department of Orthopaedic Surgery, Aarhus University Hospital, Aarhus, Denmark.
Background:
Peri and postoperative antibiotics are key adjuvant treatment tools in the management of periprosthetic joint infection (PJI). The aim of this study was to evaluate the effect of rifampicin on the area under the moxifloxacin concentration-time curve from 0 to 24 hours (AUC0-24) in the synovial fluid of the knee joint, tibial bone, and adjacent subcutaneous tissue under steady-state conditions using microdialysis in a porcine model.
Methods:
Twenty female pigs were randomized to receive oral treatment with moxifloxacin monotherapy (Group A, n = 10) of 400 mg once daily for 3 days or a combination therapy (Group B, n = 10) of 400 mg of moxifloxacin once daily for 3 days and 450 mg of rifampicin twice daily for 7 days. Microdialysis was used for sampling the synovial fluid of the knee joint, tibial cancellous and cortical bone, and adjacent subcutaneous tissues. Plasma samples were taken as a reference. Measurements were obtained for 24 hours.
Results:
Coadministration of moxifloxacin and rifampicin resulted in reductions of the moxifloxacin AUC0-24 in all targeted tissue compartments by 67% to 85% (p < 0.05). The corresponding change in plasma was 20% (p = 0.49). For both groups, the tissue penetration (the ratio of tissue free fraction AUC0-24 to plasma free fraction AUC0-24 [fAUCtissue/fAUCplasma]) was incomplete in all investigated compartments. The highest moxifloxacin tissue penetration was in the knee joint synovial fluid: 0.59 (Group A) and 0.24 (Group B). The lowest tissue penetration was in the cortical bone: 0.17 (Group A) and 0.03 (Group B).
Conclusions:
We found a significant reduction of the moxifloxacin concentration, expressed as the AUC0-24, in tissues relevant to acute PJI treatment when coadministered with rifampicin.
Clinical Relevance:
The concentrations within the targeted tissue compartments were reduced significantly more than the concentrations in plasma, which may be particularly important as plasma concentrations are used in clinical practice to assess moxifloxacin treatment sufficiency.
Insights
Rifampicin significantly reduces moxifloxacin concentrations in tissues relevant to periprosthetic joint infection (PJI) treatment. This interaction is more pronounced in tissues than in plasma, impacting treatment efficacy.
Area of Science:
- Pharmacokinetics and drug interactions in orthopedic surgery.
- Antimicrobial efficacy and tissue penetration studies.
- Biomaterial and implant-associated infection research.
Background:
- Antibiotics are crucial for managing periprosthetic joint infection (PJI).
- Understanding drug interactions is vital for optimizing PJI treatment.
- Rifampicin's effect on moxifloxacin tissue levels in PJI requires investigation.
Purpose of the Study:
- To evaluate rifampicin's impact on moxifloxacin pharmacokinetics in PJI-relevant tissues.
- To quantify moxifloxacin area under the concentration-time curve (AUC0-24) in synovial fluid, bone, and subcutaneous tissue.
- To assess tissue penetration of moxifloxacin when coadministered with rifampicin.
Main Methods:
- A porcine model was used to study drug concentrations in vivo.
- Microdialysis sampled synovial fluid, tibial bone (cancellous and cortical), and subcutaneous tissue.
- Plasma concentrations served as a reference for calculating tissue penetration.
Main Results:
- Coadministration of rifampicin reduced moxifloxacin AUC0-24 by 67-85% in all targeted tissues (p < 0.05).
- Plasma moxifloxacin AUC0-24 decreased by only 20% (p = 0.49).
- Moxifloxacin tissue penetration was incomplete, with the highest in synovial fluid (0.59 A, 0.24 B) and lowest in cortical bone (0.17 A, 0.03 B).
Conclusions:
- Rifampicin significantly reduces moxifloxacin concentrations in PJI-relevant tissues.
- The observed drug interaction may compromise moxifloxacin efficacy in treating PJI.
- Tissue concentrations decreased more than plasma concentrations, highlighting potential clinical relevance.
More Related Videos
Related Concept Videos
01:15Determination of Multiple Dosing Parameters: Steady-State, Minimum and Maximum Concentrations
01:28Inhibitors of Bacterial DNA Synthesis