Soft tissue concentrations of ciprofloxacin in obese and lean subjects following weight-adjusted dosing

OBJECTIVE: To investigate whether weight adjusted ciprofloxacin dosing resu lts 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 5 9 +/- 8.6 kg). METHODS: Sampling of interstitial space fluid by means of calibrated in viv o microdialysis after a weight-adjusted intravenous bolus dose of 2.85 mg/k g ciprofloxacin. Analysis of drug concentration by high pressure liquid chr omatography. RESULTS: We found significantly higher peak and trough levels of ciprofloxa cin in plasma for obese subjects (9.97 +/- 5.64 and 0.44 +/- 0.10 mug/ml vs 2.59 +/- 1.06 and 0.19 +/- 0.09 mug/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 ciproflox acin.