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RESEARCH PRODUCT

The Pharmacokinetics of Metronidazole and Gentamicin in a Single Preoperative Dose as Antibiotic Prophylaxis in Colorectal Surgery

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Objective: To describe, in patients undergoing colorectal surgery (CRS), the pharmacokinetics of a single, prophylactic preoperative dose of 1500 mg of metronidazole plus 240 mg gentamicin and measure its efficacy in accordance with the accepted pharmacodynamic and microbiological parameters. Method: Thirty-six patients undergoing CRS agreed to participate in the study. Three blood samples were taken from each. Cmax 15 minutes after finishing the infusion of the mixture, CfinIQ on finishing the surgery, and Cmin between 12 and 24 hours post-administration. The concentrations of metronidazole and gentamicin in each simple were measured and the pharmacokinetic parameters were estimated (dV-distribution volume, Cl-plasma clearance). For the metronidazole, concentrations in excess of 8 µg/mL were considered effective, and for gentamicin, Cmax in excess of 9 µg/mL and inhibition quotients above 8. Results: All the concentrations of metronidazole, both Cmax MTZ and CfinIQ MTZ were above 8 µg/mL and all the Cmax GEN in excess of 9 µg/mL. The ClGEN was 13.8 (3.8), with no individual value below 8. For the metronidazole, a dV of 0.68 (0.2) L/kg was estimated and a Cl of 3.15 (1.20) L/h and for the gentamicin, the dV as 0.23 (0.06) L/kg and the Cl was 4.71 (1.95) L/h. Conclusion: In patients undergoing CRS, surgical intervention did not significantly modify the pharmacokinetics of metronidazole or gentamicin in comparison with other groups of patients. The prophylaxis using a single, pre-surgical dose enables the achievement, for both antimicrobial agents, concentrations of a sufficient size to guarantee clinical efficacy.