OBJECTIVE: To investigate whether weight adjusted ciprofloxacin dosing results in comparable target site concentrations in obese and lean subjects. DESIGN: Comparative study in two populations. SUBJECTS: Twelve obese subjects (mean weight 122+/-22.6 kg, 28-52 y, male∶female ratio 4∶8) and 12 age- and sex-matched lean controls (mean weight 59+/-8.6 kg). METHODS: Sampling of interstitial space fluid by means of calibrated in vivo microdialysis after a weight-adjusted intravenous bolus dose of 2.85 mg/kg ciprofloxacin. Analysis of drug concentration by high pressure liquid chromatography. RESULTS: We found significantly higher peak and trough levels of ciprofloxacin in plasma for obese subjects (9.97+/-5.64 and 0.44+/-0.10 microg/ml vs 2.59+/-1.06 and 0.19+/-0.09 microg/ml in lean subjects, P<0.05), while concentration-time curves of interstitial fluid of muscle and subcutaneous fat did not differ between the groups. Tissue penetration, expressed as AUC(tissue)/AUC(plasma) ratio was significantly lower in obese subjects (0.45+/-0.27 vs 0.82+/-0.36, P<0.01). CONCLUSION: We conclude that the penetration process into the interstitial space fluid is impaired in obese subjects. Therefore antibiotic doses need not be adjusted for an increase in fat/water ratio. Weight-adjusted dosing based on actual body weight will yield adequate tissue levels for ciprofloxacin.
OBJECTIVE: To investigate whether weight adjusted ciprofloxacin dosing results in comparable target site concentrations in obese and lean subjects. DESIGN: Comparative study in two populations. SUBJECTS: Twelve obese subjects (mean weight 122+/-22.6 kg, 28-52 y, male&ratio;female ratio 4&ratio;8) and 12 age- and sex-matched lean controls (mean weight 59+/-8.6 kg). METHODS: Sampling of interstitial space fluid by means of calibrated in vivo microdialysis after a weight-adjusted intravenous bolus dose of 2.85 mg/kg ciprofloxacin. Analysis of drug concentration by high pressure liquid chromatography. RESULTS: We found significantly higher peak and trough levels of ciprofloxacin in plasma for obese subjects (9.97+/-5.64 and 0.44+/-0.10 microg/ml vs 2.59+/-1.06 and 0.19+/-0.09 microg/ml in lean subjects, P<0.05), while concentration-time curves of interstitial fluid of muscle and subcutaneous fat did not differ between the groups. Tissue penetration, expressed as AUC(tissue)/AUC(plasma) ratio was significantly lower in obese subjects (0.45+/-0.27 vs 0.82+/-0.36, P<0.01). CONCLUSION: We conclude that the penetration process into the interstitial space fluid is impaired in obese subjects. Therefore antibiotic doses need not be adjusted for an increase in fat/water ratio. Weight-adjusted dosing based on actual body weight will yield adequate tissue levels for ciprofloxacin.
Authors: Teena Chopra; Jing J Zhao; George Alangaden; Michael H Wood; Keith S Kaye Journal: Expert Rev Pharmacoecon Outcomes Res Date: 2010-06 Impact factor: 2.217