Prediction of bone penetration and efficacies of five fluoroquinolone antibiotics in the treatment of pseudomonal chronic osteomyelitis using a rat model

Date of Completion

January 1991


Health Sciences, Pharmacy




A systematic study of the fluoroquinolone antibiotics was conducted to investigate the factors that can be used to predict penetration of five fluoroquinolone antibiotics (ciprofloxacin, pefloxacin, fleroxacin, ofloxacin and lomefloxacin) into infected tibia bone of rats, and to correlate drug effectiveness with bone penetration.^ The hypothesis to be tested in this study is that penetration of fluoroquinolone antibiotics into bone is related to the volume of distribution of a drug, in vitro apparent partition coefficient, and total body clearance. The hypothesis was tested in a rat chronic osteomyelitis model.^ In-vitro apparent partition coefficient of these antibiotics was determined using an oil-in-water system, volume of distribution and total body clearance were obtained in the infected animals after a single IV bolus dose, and the penetration ratio of antibiotics into infected tibia bone was determined after a single IP dose. Efficacy of antibiotic treatment was determined after 28 days of treatment. The following order of antibiotic efficacy was observed: ciprofloxacin has the best efficacy, then lomefloxacin, ofloxacin, pefloxacin, and fleroxacin has the worst efficacy in the treatment of Pseudomonal chronic osteomyelitis. The results of the study suggested that the in vivo penetration ratio (PR) can be predicted using a combination of total body clearance (Cl$\sb{\rm T}$) and apparent partition coefficient as indicated by stepwise comparison analysis. A better bone penetration of fluoroquinolone antibiotics should result in better efficacy. In addition, a sigmoidal relationship is observed between efficacy and bone penetration. Finally, the efficacy of antibiotic treatment and area under the bone concentration-time curve can also be described by a sigmoidal relationship using the Hill equation. ^