摘要
目的:根据抗菌药物PK/PD理论,采用蒙特卡罗模拟的手段,对肾功能不全患者万古霉素的给药方案进行优化。方法:收集已发表的万古霉素的药代动力学资料和我院万古霉素对甲氧西林耐药金黄色葡萄球菌(MRSA)的MIC分布数据;设置AUC24 h/MIC>400,利用Crystal Ball软件模拟出5 000例患者的PTA和CFR。并与临床病例进行对照。结果:万古霉素能达到满意抗菌活性的最低剂量:对于肌酐清除率>80 mL.min-1的患者(A组),当MIC=0.5μg.mL-1时,给予万古霉素1 500 mg.d-1;当MIC=1μg.mL-1时,给予万古霉素2 500 mg.d-1;当MIC=2或4μg.mL-1时,即使给予万古霉素4 000 mg.d-1,也不能达到满意的抗菌活性。对于肌酐清除率在50～80 mL.min-1的患者,当MIC=0.5μg.mL-1时,给予万古霉素1 000mg.d-1,当MIC=1μg.mL-1时,给予万古霉素2 000 mg.d-1;当MIC=2或4μg.mL-1时,即使给予万古霉素2 000 mg.d-1,也不能达到满意的抗菌活性。对于肌酐清除率在10～50 mL.min-1的患者,只有在MIC=0.5μg.mL-1时给予750 mg.d-1,才能达到满意的抗菌活性;对于健康志愿者,当MIC=0.5μg.mL-1时,给予万古霉素2 000 mg.d-1,能达到满意的抗菌活性。临床结果与模拟结果基本一致。结论:蒙特卡罗模拟法把药代动力学和药效学结合起来,既考虑了不同个体对药物处置的差异性,又考虑了病原菌耐药性的差异,这样获得的给药方案将更合理,也更能提高临床治疗效果。
Objective： To optimize vancomycin dosing regimens in MRSA-infected patients with renal dysfunction using Monte Carlo simulation according to PK/PD theory for antibiotics. Methods： The population pharmacokinetic data of vancomycin reported previously and the MIC distribution for vancomycin against MRSA in our hospital were collected and used to set up AUC24 JMIC 〉 400. The PTA and CFR of 5 000 patients were simulated using Crystal Ball software, and compared with the clinically collected cases. Results ： The lowest dose of vancomyein with satisfactory antibacterial activity was as follows. When CLCR is 〉 80 mL· min- 1 , if MIC = 0.5 μg· mL^-1 , vancomycin dosage will be 1 500 mg· d - 1 ; while if MIC = 1 μg· mL^-1, vancomycin dosage will be 2 500 mg· d -1 When CLCR is 50 - 80 mL· min -1, if MIC = 0.5 μg· mL^-1 , vancomycin dosage will be 1 000 mg· d - 1 ; if MIC = 1 μg· mL^-1 , vancomycin dosage will be 2 000 mg·d-1. When CLCR is 10 -50 mL·min-1 , if MIC =0.5 μg· mL^-1 ,vancomycin dosage will be 750 mg- d-1. For healthy volunteers, if MIC = 0.5 μg· mL^-1, vancomycin dosage will be 2 000 mg· d - 1. The simulated results were basically agree with clinical results. Conclusion ： Designing of dosage regimen based on Monte Carlo simulation is reasonable and valid because this method has taken the difference be- tween individuals into full account.
出处
《中国新药杂志》
CAS
CSCD
北大核心
2012年第3期335-338,共4页
Chinese Journal of New Drugs
