Population Pharmacokinetic Model-Based Evaluation of Standard Dosing Regimens for Cefuroxime Used in Coronary Artery Bypass Graft Surgery with Cardiopulmonary Bypass.
The purpose of this study was to investigate the population pharmacokinetics (PK) of cefuroxime in patients undergoing coronary artery bypass graft (CABG) surgery. In this observational pharmacokinetic study, multiple blood samples were collected over a 48-h interval of intravenous cefuroxime administration. The samples were analyzed by using a validated high-performance liquid chromatography (HPLC) method. Population pharmacokinetic models were developed using Monolix (version 4.4) software. Pharmacokinetic-pharmacodynamic (PD) simulations were performed to explore the ability of different dosage regimens to achieve the pharmacodynamic targets. A total of 468 blood samples from 78 patients were analyzed. The PK for cefuroxime were best described by a two-compartment model with between-subject variability on clearance, the volume of distribution of the central compartment, and the volume of distribution of the peripheral compartment. The clearance of cefuroxime was related to creatinine clearance (CLCR). Dosing simulations showed that standard dosing regimens of 1.5 g could achieve the PK-PD target of the percentage of the time that the free concentration is maintained above the MIC during a dosing interval (fTMIC) of 65% for an MIC of 8 mg/liter in patients with a CLCR of 30, 60, or 90 ml/min, whereas this dosing regimen failed to achieve the PK-PD target in patients with a CLCR of ≥125 ml/min. In conclusion, administration of standard doses of 1.5 g three times daily provided adequate antibiotic prophylaxis in patients undergoing CABG surgery. Lower doses failed to achieve the PK-PD target. Patients with high CLCR values required either higher doses or shorter intervals of cefuroxime dosing. On the other hand, lower doses (1 g three times daily) produced adequate target attainment for patients with low CLCR values (≤30 ml/min).
['Alqahtani|Saeed A|SA|', 'Alsultan|Abdullah S|AS|', 'Alqattan|Hussain M|HM|', 'Eldemerdash|Ahmed|A|', 'Albacker|Turki B|TB|']
D000293:Adolescent D000328:Adult D000368:Aged D000369:Aged, 80 and over D000900:Anti-Bacterial Agents D002315:Cardiopulmonary Bypass D002444:Cefuroxime D002851:Chromatography, High Pressure Liquid D001026:Coronary Artery Bypass D005260:Female D006801:Humans D008297:Male D008826:Microbial Sensitivity Tests D008875:Middle Aged D009010:Monte Carlo Method D055815:Young Adult D047090:beta-Lactams
cefuroxime CABG antibiotic prophylaxis Monte Carlo simulation pharmacokinetics-pharmacodynamics population PK β-lactams