Soft tissue concentrations of ciprofloxacin in obese and lean subjects following weight-adjusted dosing.
OBJECTIVE
To investigate whether weight adjusted ciprofloxacin dosing results in comparable target site concentrations in obese and lean subjects.


METHODS
Comparative study in two populations.


METHODS
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).


CONCLUSIONS
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.
Hollenstein
U M
UM
Department of Clinical Pharmacology, Vienna University Hospital, Vienna, Austria.
Brunner
M
M
Schmid
R
R
Müller
M
M
D000328:Adult; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D005110:Extracellular Space / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*
D000890:Anti-Infective Agents; D002939:Ciprofloxacin