基于新型肾功能标志物的中国成人万古霉素群体药物动力学模型的建立与给药方案的优化

耐甲氧西林葡萄球菌（MRS）是我国细菌耐药的突出问题。万古霉素是治疗MRS感染的首选药物，但其治疗窗很窄,剂量过高引起肾毒性,剂量过低导致治疗失败甚至细菌耐药的产生。我们前期的研究建立了中国成人万古霉素群体药物动力学模型，并初步实现个体化给药。但由于血清肌酐（creatinine，Cr）作为肾功能的标志物的局限性使该模型尚需改进。本项目拟进一步研究新型肾功能标志物胱抑素C（CysC）、β痕迹蛋白（BTP）与万古霉素清除率的关系，用NONMEM方法建立基于新型肾功能标志物的中国成人万古霉素群体药物动力学模型，通过蒙特卡洛仿真法优化给药方案，并检测患者血清中CysC 、BTP、尿中肾损伤分子-1（KIM-1）、中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、白介素-18 (IL-18)等新型肾功能标志物的含量变化探讨万古霉素对肾功能的影响，为临床万古霉素个体化治疗和新治疗方案提供依据。

Methicillin resistant Staphylococcus (MRS) is a prominent　bacterial resistantce issue in China. Vancomycin still remains the treatment of choice for MRS infections.But Vancomycin has a narrow therapeutic range, high doses are associated with nephrotoxicity, low doses cause even treatment failure or the emergence of reduced vancomycin susceptibility. We previous repoted a vancomycin population pharmacokinetic model for Chinese adult patients, and realized the preliminary individual therapy. The model still needs to be improved because the serum creatinine (creatinine, Cr) limitations as the renal function biomarker. Our research aim to improve the relation between vancomycin clearance and cystatin C (CysC)or beta trace protein (BTP), build a population pharmacokinetic model by NONMEM for Chinese adult patients using novel renal function biomarkers and develop initial dosage regimens for patients with different degrees of renal function using Monte Carlo simulation. The concentration of CysC and BTP in serum, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL)and interleukin-18 (IL-18)in urine will be determined to identify the relation of vancomycin and renal function. The purpose of this research is to provide some help for individual therapy and new treatment options in vancomycin.