目的:探讨影响万古霉素、哌拉西林/他唑巴坦、美罗培南3种药物治疗药物监测(therapeutic drug monitoring,TDM)靶值和药动学/药效学(pharmacokinetic/pharmacodynamic,PK/PD)靶值未达标的危险因素以及2种靶值和微生物疗效的关系,为精准...目的:探讨影响万古霉素、哌拉西林/他唑巴坦、美罗培南3种药物治疗药物监测(therapeutic drug monitoring,TDM)靶值和药动学/药效学(pharmacokinetic/pharmacodynamic,PK/PD)靶值未达标的危险因素以及2种靶值和微生物疗效的关系,为精准用药提供科学依据。方法:纳入2021年3月至2022年3月接受万古霉素、哌拉西林/他唑巴坦、美罗培南中至少1种抗菌药物联合治疗的危重症患者。利用优化采样方案采集每位患者的3~4份血浆样本,借助非房室模型结合经典药动学理论计算PK/PD参数。采用多因素分析探究3种药物TDM靶值和PK/PD靶值未达标的相关危险因素。结果:共纳入接受万古霉素、哌拉西林/他唑巴坦或美罗培南治疗的25名危重症患者的96份血浆样本,共计151份血药浓度-时间数据。万古霉素、哌拉西林/他唑巴坦和美罗培南的谷浓度(trough concentration,Cmin)达标率低,分别为20.00%、22.22%和23.53%;万古霉素PK/PD靶值达标率、未达标率和超标率分别为20.00%、60.00%和20.00%。哌拉西林/他唑巴坦和美罗培南的PK/PD靶值达标率分别为11.11%和17.65%,未达标率分别高达88.89%和76.47%。影响因素探究发现肌酐清除率是影响3种抗菌药物Cmin和PK/PD靶值不达标的独立危险因素。细菌根除组患者的万古霉素Cmin[(15.329±7.522)mg·L^(-1)vs.(6.273±0.754)mg·L^(-1),P=0.019]和AUC0~24 h/MIC(578.47±413.86 vs.175.94±17.07,P=0.028)均显著高于细菌未根除组。结论:万古霉素、哌拉西林/他唑巴坦、美罗培南在危重症患者中的TDM靶值和PK/PD靶值达标率低,未达标率高,普遍存在低暴露和过暴露情况。提高TDM靶值和PK/PD靶值达标率均可能提高患者细菌根除率,因此十分有必要在此类患者中开展TDM,为精准给药提供参考。展开更多
Objection： To study the relationship between different doses and biological effect of 32p-glass microspheres （32P-GMS） by percutaneous intra-tumor injection at different times and provide proofs of theory for clini...Objection： To study the relationship between different doses and biological effect of 32p-glass microspheres （32P-GMS） by percutaneous intra-tumor injection at different times and provide proofs of theory for clinical therapy. Methods： 36 Zealand rabbits and Vx-2 were used to establish the animal model of liver tumor. Six groups were randomly designed. The suspension of different radiative doses of 32p-GMS combined with lipiodol-ultrafluid （0.1 mL） was respectively injected by percutaneous intra-tumor. The tumor tissues were examined by light microscope. MRI examination of liver tumors were performed before and after the injection. Results： C and D groups were observed that the tumor volume was decreased and the rate of restrained tumor was gradually increased after injection of 32p-GMS. The living tumor tissues of E group completely disappeared after the injection for two weeks. MRI examination showed that the tumor signal of E group was equal as T2 as the signal of normal liver parenchyma. The living tumor tissues were not found in F group after the injection for three weeks. Conclusion： 111 MBq was the best radiative dose of ~2p-GMS for treatment of 1 cm liver cancer by percutaneous intra-tumor injection. MRI examination was very valuable to evaluate the result and follow up after the injection to treat liver cancer.展开更多
基金a grant from the Tianjin Municipal Commission of Science and Technology(No.003607111)
文摘Objection： To study the relationship between different doses and biological effect of 32p-glass microspheres （32P-GMS） by percutaneous intra-tumor injection at different times and provide proofs of theory for clinical therapy. Methods： 36 Zealand rabbits and Vx-2 were used to establish the animal model of liver tumor. Six groups were randomly designed. The suspension of different radiative doses of 32p-GMS combined with lipiodol-ultrafluid （0.1 mL） was respectively injected by percutaneous intra-tumor. The tumor tissues were examined by light microscope. MRI examination of liver tumors were performed before and after the injection. Results： C and D groups were observed that the tumor volume was decreased and the rate of restrained tumor was gradually increased after injection of 32p-GMS. The living tumor tissues of E group completely disappeared after the injection for two weeks. MRI examination showed that the tumor signal of E group was equal as T2 as the signal of normal liver parenchyma. The living tumor tissues were not found in F group after the injection for three weeks. Conclusion： 111 MBq was the best radiative dose of ~2p-GMS for treatment of 1 cm liver cancer by percutaneous intra-tumor injection. MRI examination was very valuable to evaluate the result and follow up after the injection to treat liver cancer.
