【作者】 经力； 刘滔滔； 郭晴； 庞惠媚； 韦文兴； 覃小玲； 陈铭； 张韧；

【机构】 广西医科大学第一附属医院药学部；

【摘要】 背景和目的:万古霉素已经在临床上使用多年,关于它已有很多群体药代动力学研究的报道。然而,对于它在神经外科术后病人中应用的研究却相对较少。因此本研究的主要目标是探索万古霉素在这部分人群中的动力学是否与其它患者一致,以及尝试验证新的剂量方案是否合适这部分病人。方式:收集在广西医科大学第一附属医院住院并静脉使用万古霉素的342名患者,共650个血药浓度点。这些病人根据是否接受神经外科手术被分为手术组和非手术组。之后将模型的动力学参数固定为最终模型的参数,并通过交互的一级条件评估方式获得每个患者的药代动力学参数。利用这些参数并结合贝叶斯反馈,当新的剂量方案和专家共识推荐的剂量方案分别在这部分患者中模拟使用时,即可获得预测的万古霉素谷浓度。结果:对于非手术病人,患者预测的CL是4.20 L·h^-1,万古霉素实测谷浓度在<10 mg/L和15-20 mg/L范围内的比例分别为32.1%和20.6%。对于手术病人,患者通过贝叶斯法预测得到的清除率（CL）为5.62 L·h^-1,万古霉素实测谷浓度在<10 mg/L和15-20 mg/L范围内的比例分别为58.9%和8.5%。当新的万古霉素剂量方案在手术病人中被模拟使用时,模拟得到的万古霉素谷浓度在<10 mg/L和15-20 mg/L范围内的比例分别为37.2%和16.7%。当专家共识推荐的剂量方案在手术组患者中模拟使用时,模拟得到的万古霉素谷浓度在<10 mg/L和15-20 mg/L范围内的比例分别为53.8%和5.8%。结论:与非手术的患者相比,神经外科手术患者预测得到的万古霉素清除率更高。此外,与专家共识推荐的剂量相比,当新剂量方案在手术病人中被模拟使用时,在>10 mg·L^-1的范围内有更高比例的万古霉素谷浓度,但剂量仍不足以使大部分神经外科术后患者的谷浓度达到15-20 mg·L^-1目标浓度。更多还原

【Abstract】 Background and Objective Vancomycin have been used for a long time in clinical and there are numerous reported studies on population pharmacokinetic of vancomycin.However, there are few researches for patients with a neurosurgery operative. The main aim of this study wasexploring whether pharmacokinetic of vancomycin was different in these patientsand trying tovalidatedwhether newvancomycin dose regimenwasappropriatefor them.Method A dataset included 650 serum concentration points from 342 patients who received vancomycin intravenouslywere used.These patients were distinguished into surgerygroup and non-surgerygroupbased on whether patients undergoing a neurosurgery operative or not. Patients’ estimated individual parameter were obtained usingfirst order conditional estimation with interaction throughfixing the parameters of model to those from the previously reported model（NONMEM MAXEVAL = 0 POSTHOC）.Then, these estimated individual parameters were used to predict vancomycin trough concentrations using Bayes methods when the current and new dosage guidelines were simulated used,respectively.Results In non-surgerygroup, the simulated CL value was 4.20 L·h^-1 and the proportion of observed vancomycin troughs concentrations within <10 mg/L and 15-20 mg/L were 32.1% and 20.6%, respectively.In surgerygroup, the value of simulated clearance（CL）was 5.62 L/h and the proportion of vancomycin troughs concentrations within <10 mg/L and 15-20 mg/L were 58.9% and8.5%, respectively.When new dosage guidelines were simulated in the surgery group patients, the proportion of predictedvancomycin trough concentrations within < 10 mg/L and 15-20 mg/L was 37.2% and 16.7%,respectively.When current dosage guidelineswere simulated used in these patients, the proportion of predictedvancomycin trough concentrations within < 10 mg/L and 15-20 mg/L was 53.8% and 5.8%, respectively.Conclusions Surgery group patients have higher predicted vancomycin clearance than non-surgerygroup patients.Besides, in surgery group, there are a higher proportion of predicted vancomycin trough within the range >10 mg·L^-1 when new dose regimen was simulated used than current dosage regimen was simulated used, butthe dose is still not enoughfor most postoperative neurosurgical patients to achieve a target concentration of 15-20 mg·L^-1.更多还原