Perioperative penetration of metronidazole into muscle tissue: a microdialysis study.
OBJECTIVE
To evaluate the concentration of metronidazole in muscle tissue using microdialysis and to compare it with plasma concentration and in vitro-defined MIC(90) (minimal inhibiting concentration) for the most frequent anaerobic bacteria isolated in our hospital.


METHODS
Six female patients scheduled for elective gynaecological surgery were included. Exclusion criteria were active inflammatory process and being overweight (BMI more than 30). Microdialysis catheters (CMA 60 catheters with 20 kDa cut-off membrane) were placed into the m. vastus lateralis. The microdialysis perfusion rate was 2 microl/min. To assess in vivo recovery of the drug, retrodialysis with a 5-mg/l solution of metronidazole was performed. Microdialysis and blood samples were collected simultaneously 10 h after metronidazole administration. MIC(90) data were obtained from the database of the microbiology laboratory of the local hospital.


RESULTS
Data from five patients were included in analysis. The metronidazole concentration in blood achieved a value of 16.5+/-4.6 mg/l at 30 min (first available data), while in muscle a maximum level of 7.8+/-1.5 mg/l was achieved at 114 min. The mean MIC(90) for the Bacteroides fragilis group was 0.25+/-0.26 mg/l. Data from mean plasma concentrations were fitted into the two-compartmental model and time over MIC(90) and time over four times MIC(90) were calculated, which were 52.1+/-13.5 h and 33.2+/-8.7 h, respectively. The C(max)/MIC(90) ratio was 65.8+/-18.5 for plasma and 31.1+/-6.2 for muscle.


CONCLUSIONS
The present data demonstrate that metronidazole penetrates well into muscle tissue. Muscle tissue concentrations reach values far greater than MIC(90) for the Bacteroides fragilis group and persist at such high levels for at least 10 h.
Karjagin
Juri
J
Anaesthesiology and Intensive Care Clinic, University of Tartu, Puusepa Street 8, 51014 Tartu, Estonia. jyrika@kliinikum.ee
Pähkla
Rein
R
Starkopf
Joel
J
D000328:Adult; D000890:Anti-Infective Agents / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001441:Bacteroides fragilis / Q000187:drug effects / Q000302:isolation & purification; D005260:Female; D006207:Half-Life; D006801:Humans; D008795:Metronidazole / Q000097:blood / Q000493:pharmacokinetics*; D008826:Microbial Sensitivity Tests; D017551:Microdialysis; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D014018:Tissue Distribution
D000890:Anti-Infective Agents; D008795:Metronidazole