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.


METHODS
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 micromol/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.


CONCLUSIONS
Use of cutaneous microdialysis technique permits the characterization of true systemic drug disposition, for optimizing drug treatment strategies.
Bielecka-Grzela
S
S
Dermatopharmacotherapy Division, Department of Dermatology, Pomeranian Medical University, Szczecin, Poland. adklim@sci.pam.szczecin.pl
Klimowicz
A
A
D000284:Administration, Oral; D000890:Anti-Infective Agents / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D008297:Male; D008795:Metronidazole / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D017551:Microdialysis / Q000379:methods*; D012867:Skin / Q000378:metabolism
D000890:Anti-Infective Agents; D008795:Metronidazole