Pharmacokinetics and tissue penetration of a single 1,000-milligram, intravenous dose of metronidazole for antibiotic prophylaxis of colorectal surgery.
The levels of metronidazole in serum and tissue penetration of metronidazole were studied after prophylactic administration in 11 patients undergoing elective colorectal surgery. A single dose of 1,000 mg given intravenously was administered before surgery. Adequate drug levels in serum (greater than or equal to MIC for 90% of strains tested [MIC90] for Bacteroides fragilis) were found in all patients throughout the procedure. Mean peak (15-min) and last-determined (24-h) metronidazole levels in serum were 28.8 +/- 8 and 4.2 +/- 1.7 mg/liter, respectively. The beta-phase elimination half-life was 9.5 +/- 2.3 h, and the clearance and apparent volume of distribution were 57 +/- 13 ml/min and 0.7 +/- 0.1 liter/kg, respectively. In the colonic wall at surgical anastomosis, tissue metronidazole levels greater than or equal to MIC90 for B. fragilis were found in 91% of patients. In the abdominal wall fat and epiploic fat, tissue metronidazole levels greater than or equal to MIC90 for B. fragilis were found in 40 to 60% of patients at surgical incision and closure. No anaerobic infection occurred during the study.
Martin
C
C
Department of Anesthesia and Intensive Care, Sainte Marguerite Hospital, Marseille, France.
Sastre
B
B
Mallet
M N
MN
Bruguerolle
B
B
Brun
J P
JP
De Micco
P
P
Gouin
F
F
D000368:Aged; D001441:Bacteroides fragilis / Q000187:drug effects; D003106:Colon / Q000601:surgery*; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007432:Intraoperative Period; D008297:Male; D008795:Metronidazole / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008875:Middle Aged; D011292:Premedication; D012007:Rectum / Q000601:surgery*; D014018:Tissue Distribution
D008795:Metronidazole