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

Abstract

OBJECTIVE: To investigate whether weight adjusted cipro¯oxacin 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 AE 22.6 kg, 28 ± 52 y, maleXfemale ratio 4X8) and 12 age-and sex-matched lean controls (mean weight 59 AE 8.6 kg). METHODS: Sampling of interstitial space¯uid by means of calibrated in vivo microdialysis after a weight-adjusted intravenous bolus dose of 2.85 mgakg cipro¯oxacin. Analysis of drug concentration by high pressure liquid chromatography. RESULTS: We found signi®cantly higher peak and trough levels of cipro¯oxacin in plasma for obese subjects (9.97 AE 5.64 and 0.44 AE 0.10 mgaml vs 2.59 AE 1.06 and 0.19 AE 0.09 mgaml in lean subjects, P`0.05), while concentration ± time curves of interstitial¯uid of muscle and subcutaneous fat did not differ between the groups. Tissue penetration, expressed as AUC tissue aAUC plasma ratio was signi®cantly lower in obese subjects (0.45 AE 0.27 vs 0.82 AE 0.36, P`0.01). CONCLUSION: We conclude that the penetration process into the interstitial space¯uid is impaired in obese subjects. Therefore antibiotic doses need not be adjusted for an increase in fatawater ratio. Weight-adjusted dosing based on actual body weight will yield adequate tissue levels for cipro¯oxacin.

Issues in Pharmacokinetics and Pharmacodynamics of Anti-Infective Agents: Distribution in Tissue

“…Thus, the process of penetration into the ISF is markedly impaired in obese subjects, most likely because of a reduced capillary permeability surface area in fat tissue (72).…”

“…Recently, Hollenstein et al (72) addressed the issue of tissue penetration of ciprofloxacin in obese subjects with a mean weight of 122 kg and age-and sex-matched lean control subjects and found ϳ50% lower tissue AUC/plasma AUC ratios in obese subjects. Thus, the process of penetration into the ISF is markedly impaired in obese subjects, most likely because of a reduced capillary permeability surface area in fat tissue (72).…”

Factors Influencing the Use and Interpretation of Animal Models in the Development of Parenteral Drug Delivery Systems

“…The comparative steady state volumes of distribution (expressed as liters), when corrected for kilogram body weight, were similar, indicating that the overall distribution volume was markedly lower in obese than in lean subjects. This difference in drug distribution volume was concluded to reflect differences in the capillary surface to tissue volume ratio and accordingly, lower tissue perfusion in the obese versus lean subjects (30).…”

Influence of Morbid Obesity on the Single-Dose Pharmacokinetics of Daptomycin

“…These projections are cause for concern given that obesity is considered to be an independent risk factor for morbidity and mortality among surgical and critically ill patients (1,18,19). This emerging population poses a significant challenge to clinicians when considering antimicrobial dosing for prophylaxis and treatment of surgical site infections (12,15).…”