Population pharmacokinetic models for cefuroxime and metronidazole used in combination as prophylactic agents in colorectal surgery: Model-based evaluation of standard dosing regimens

International Journal of Antimicrobial Agents
Eduardo Asín-PrietoArantxazu Isla

Abstract

The antibiotics used for prophylaxis in colorectal surgery must maintain appropriate plasma concentrations during the entire surgery to avoid surgical site infections caused by aerobes and anaerobes; cefuroxime plus metronidazole is one of the combinations used. The aim of this study was to evaluate the adequacy of cefuroxime plus metronidazole administration as prophylaxis in colorectal surgery. In total, 63 patients electively undergoing rectal or colon surgery were administered 1500mg of cefuroxime and 1500mg of metronidazole in 15-min and 1-h infusions, respectively, prior to surgery. Blood samples were withdrawn during and after surgery for determination of plasma concentrations by high-performance liquid chromatography. Population pharmacokinetic models were developed using NONMEM 7.2.0. Pharmacokinetic/pharmacodynamic (PK/PD) simulations were performed to explore the ability of different dosage regimens to achieve the pharmacodynamic targets. Pharmacokinetics for both antibiotics were best described by a two-compartment model. Elimination of cefuroxime was conditioned by creatinine clearance (CLCr). The half-life of cefuroxime was 1.5h for patients with normal renal function and 4.9h in patients with renal impairment. El...Continue Reading

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Citations

Mar 5, 2015·Journal of Infection and Chemotherapy : Official Journal of the Japan Society of Chemotherapy·Eduardo Asín-PrietoArantxazu Isla
Jul 13, 2016·The Journal of Antimicrobial Chemotherapy·S A ZelenitskyG G Zhanel
Dec 15, 2015·Expert Opinion on Drug Metabolism & Toxicology·Sherwin K B SyHartmut Derendorf
Aug 29, 2020·Journal of Biomolecular Structure & Dynamics·Ramazan Kalinİlhami Gülçin
Dec 7, 2018·European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology·Andrew KirbyDermot Burke
Sep 21, 2021·The Journal of Antimicrobial Chemotherapy·M J J da Silva NetoA H Thomson

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