Penetration of ciprofloxacin and its desethylenemetabolite into skin in humans after a single oral dose of the parent drug assessed by cutaneous microdialysis

Abstract

To measure the concentration of ciprofloxacin and its desethylenemetabolite in plasma and cutaneous microdialysates and to compare ciprofloxacin penetration into cutaneous microdialysates against theoretically predicted penetration in a peripheral compartment. A single oral dose of 0.5 g of the parent drug was administered to 10 healthy male volunteers. Microdialysis probes with 2 kDa molecular weight cut-off were inserted intradermally and were perfused with Ringer solution up to 8 h after drug ingestion. Drug and metabolite concentrations were measured by high performance liquid chromatography. Mean maximum concentrations of ciprofloxacin in plasma, cutaneous microdialysates and theoretical peripheral compartment were 7.01+/-1.69, 2.95+/-0.64 and 3.37+/-0.60 micromol/L, respectively, and were achieved after about 2.0+/-0.6, 2.4+/-0.9 and 4.8+/-0.9 h. The extent of penetration into cutaneous microdialysates and theoretical peripheral compartment relative to plasma were 0.550+/-0.150 and 0.788+/-0.131, respectively, and differed significantly. Similarly, time to maximum concentration as well as area under the concentration-time curve in these compartments also differed significantly unlike the maximum concentration. Microdialysis permits the evaluation of the penetration of drug and its metabolites into target tissues. Such evaluation is helpful to optimize treatment strategies. After a single 0.5 g oral dose, ciprofloxacin penetrated into skin and achieved concentrations above the minimum inhibitory concentrations for susceptible pathogens, recommended by the National Committee for Clinical Laboratory Standards (NCCLS).