Application of cutaneous microdialysis to evaluate metronidazole and its main metabolite concentrations in the skin after a single oral dose

Objective: To measure the concentration of metronidazole and its hydroxymetabolite in plasma and cutaneous microdialysates and to compare metronidazole penetration into cutaneous microdialysates against theoretical predicted penetration in a peripheral compartment. Method: A single oral dose of 2 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 concentration in plasma, cutaneous microdialysates and theoretical peripheral compartment were 214 +/- 49, 151 +/- 52 and 146 +/- 38 mumol/L, respectively, and were achieved after about 2.1 +/- 0.8, 2.8 +/- 1.0 and 6.0 +/- 2.9 h. The extent of penetration into cutaneous microdialysates and theoretical peripheral compartment relative to plasma were 0.672 +/- 0.196 and 0.675 +/-0.207, respectively, and did not differ significantly. Moreover, maximum concentration as well as area under concentration-time curve in these compartments also did not differ significantly. Conclusion: Use of cutaneous microdialysis technique permits the characterization of true systemic drug disposition, for optimizing drug treatment strategies.