Pharmacokinetics and PK/PD Modeling Laboratory, Pharmaceutical Sciences Graduate Program, Faculty of Pharmacy, Federal University of Rio Grande do Sul, Av. Ipiranga, 2752, Porto Alegre, RS, 90.610-000, Brazil.
Center for Obese Class III Care, Nossa Senhora Conceição Hospital (HNSC), Porto Alegre, RS, Brazil.
Pharm Res. 2018 Apr 11;35(6):116. doi: 10.1007/s11095-018-2394-5.
To determine the efficacious cefazolin prophylactic dose for bariatric surgery using free subcutaneous concentrations accessed by microdialysis after 2 g or 3 g i.v. bolus dosing to morbidly obese women and POPPK modeling.
A POPPK model with variable plasma and subcutaneous tissue protein binding was developed to simultaneously describe plasma and tissue data sets. The outcomes was predicted for common surgical site infection (SSI) bacteria over 3, 4, 5 and 6 h periods postdose, as probability of target attainment (PTA) using Monte Carlo simulation.
CFZ 2 g warrant up to 5 h SSI prophylaxis for bacteria with MICs ≤1 mg/L such as Escherichia coli and Staphylococcus aureus. For species such as Klebsiella pneumoniae, which present MIC distribution frequency of 2 mg/L, the maintenance of PTA ≥ 90% occurs with a 3 g dose for surgeries lasting up to 5 h, and 2 g dose provide an adequate response up to 4 h (PTA of 89%).
Effectiveness of CFZ 2 g is similar to 3 g against bacteria with a MIC up to 2 mg/L, especially if the surgery does not last for more than 4 h.
通过对病态肥胖女性进行静脉推注 2g 或 3g 头孢唑林后，利用微透析法获取的游离皮下浓度，采用 POPPK 模型来确定用于肥胖症手术预防的头孢唑林有效剂量。
建立了一个具有可变血浆和皮下组织蛋白结合的 POPPK 模型，以同时描述血浆和组织数据集。使用蒙特卡罗模拟，针对术后 3、4、5 和 6 小时的常见手术部位感染（SSI）细菌，将结局预测为目标达到率（PTA）。
对于 MICs≤1mg/L 的细菌，如大肠杆菌和金黄色葡萄球菌，头孢唑林 2g 可保证长达 5 小时的 SSI 预防。对于 MIC 分布频率为 2mg/L 的细菌，如肺炎克雷伯菌，在手术持续时间不超过 5 小时的情况下，使用 3g 剂量可维持 PTA≥90%，而在 4 小时内，2g 剂量即可提供足够的反应（PTA 为 89%）。
头孢唑林 2g 的有效性与 3g 相似，可预防 MIC 不超过 2mg/L 的细菌感染，尤其是手术持续时间不超过 4 小时的情况下。
