Population Pharmacokinetic Model of Rifampicin in Staphylococcal Osteoarticular Infections

Condition(s) studied

Investigational drug(s) / intervention(s)

This study focuses on the pharmacokinetics of rifampicin and levofloxacin or ciprofloxacin, which are used in the treatment of osteoarticular infections caused by susceptible staphylococci as part of: This study primarily aims to evaluate the pharmacokinetics of rifampicin, but also of one of the two partner antibiotics, levofloxacin or ciprofloxacin, used in the treatment of staphylococcal osteoarticular infections, whether or not they are present in the body. To this end, 12 blood samples, totaling 60 ml per patient, will be required. These samples will be collected specifically for this clinical research. The remainder of the study will be conducted as part of standard patient care.

Study summary

Staphylococcal osteoarticular infections (OAIs), including prosthetic joint infections and chronic osteomyelitis, represent a major cause of morbidity. Rifampicin is a key bactericidal antibiotic effective against staphylococcal biofilm. However, its pharmacokinetics exhibit substantial inter-individual variability due to complex hepatic metabolism and drug interactions. Currently, no prospective population pharmacokinetic (PopPK) model of rifampicin combined with levofloxacin or ciprofloxacin exists in patients with OAIs. Objectives:

The primary objective of this study is to develop a population pharmacokinetic model of oral rifampicin in patients undergoing medico-surgical treatment for staphylococcal osteoarticular infections. Secondary objectives include evaluating the pharmacokinetics of the partner antibiotic (levofloxacin or ciprofloxacin), investigating the correlation between antibiotic exposure metrics (AUC, Cmax, AUC/MIC) and clinical/biological tolerance, and assessing 1-year infection relapse-free survival and resistance emergence. Study Design:

Prospective, single-center, interventional study with minimal risks and constraints (RIPH 2) involving 40 participants recruited at the Reference Center for Complex Osteoarticular Infections (CRIOAC).

Eligibility

Primary outcome measure(s)

• Area Under the Plasma Concentration-Time Curve (AUC) of Rifampicin — Day 2/3, Day 8/10, and Day 28/32 post-initiation of antibiotic therapy
  Area under the plasma concentration-time curve of oral rifampicin, estimated using a population pharmacokinetic non-linear mixed-effects model (NONMEM).
• Peak Plasma Concentration (Cmax) of Rifampicin — Day 2/3, Day 8/10, and Day 28/32 post-initiation of antibiotic therapy
  Maximum observed plasma concentration (Cmax) of oral rifampicin, measured following administration.
• Apparent Oral Clearance (CL/F) of Rifampicin — Through 4 weeks post-initiation of antibiotic therapy
  Apparent oral clearance (CL/F) of rifampicin estimated using a population pharmacokinetic model (NONMEM), including evaluation of inter-individual variability and covariate effects.
• Apparent Volume of Distribution (V/F) of Rifampicin — Through 4 weeks post-initiation of antibiotic therapy
  Apparent volume of distribution (V/F) of rifampicin estimated using a population pharmacokinetic model (NONMEM), including evaluation of inter-individual variability and covariate effects.

Trial sites (1)

More Groupe Hospitalier Diaconesses Croix Saint-Simon trials in France

Other trials for the same condition