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 μmol/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.