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Penetration of ciprofloxacin and its desethylenemetabolite into skin in humans after a single oral dose of the parent drug assessed by cutaneous microdialysis
Author(s) -
BieleckaGrzela S.,
Klimowicz A.
Publication year - 2005
Publication title -
journal of clinical pharmacy and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.622
H-Index - 73
eISSN - 1365-2710
pISSN - 0269-4727
DOI - 10.1111/j.1365-2710.2005.00657.x
Subject(s) - microdialysis , penetration (warfare) , pharmacokinetics , metabolite , ciprofloxacin , area under the curve , pharmacology , medicine , active metabolite , ingestion , drug , chemistry , antibiotics , biochemistry , operations research , engineering , central nervous system
Summary Objective: 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. Method: 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. Results: 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 μ mol/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. Conclusion: 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).