Pharmacokinetics of intravenous metronidazole in the plasma, peritoneal fluid, peritoneum, and subcutaneous adipose tissue of patients undergoing lower gastrointestinal surgery

INTRODUCTION Cefazolin plus metronidazole (MTZ) lowers the surgical site infection (SSI) rate. However, MTZ concentrations in plasma and various tissues during surgery remain unclear in Japanese patients. We aimed to verify the dosing regimen of prophylactic MTZ injection for colorectal surgery. METHODS Ten patients undergoing elective colorectal surgery received cefazolin (1 g) and MTZ (500 mg). Venous blood, peritoneal fluid, peritoneum, and subcutaneous adipose tissue samples were collected hourly. Pharmacokinetic parameters were estimated. Site-specific target attainment was simulated using an area under the curve (AUC) / minimum inhibitory concentration (MIC) target of 70 against Bacteroides fragilis (MIC = 2mg/L). RESULTS The AUC0-∞ values for plasma, peritoneal fluid, peritoneum, and subcutaneous tissue were 96.5 ± 54.9 mg*h/L, 89.5 ± 15.9 mg*h/L, 40.2 ± 14.0 mg*h/kg, and 17.8 ± 12.1 mg*h/kg, respectively. After a single 500-mg administration, MTZ concentrations in all tissues were predicted to be > 2 mg/kg at 6.56 h, and remain > 2 mg/kg at 8 h in plasma, peritoneal fluid, and peritoneum. Simulation showed that the MTZ 500 mg q8h regimen would achieve AUC/MIC > 70 in the peritoneal fluid and peritoneum. CONCLUSIONS This study clarifies the pharmacokinetics of MTZ in Japanese patients. A single 500-mg dose is predicted to be effective for standard colorectal procedures, while a 500-mg q8h regimen shows a favorable profile for intra-abdominal sites.