Predicting Antibiotic Effect of Vancomycin Using Pharmacokinetic/Pharmacodynamic Modeling and Simulation: Dense Sampling versus Sparse Sampling

被引:7
作者
Kim, Yong Kyun [1 ]
Lee, Jae Ha [2 ]
Jang, Hang-Jea [2 ]
Zang, Dae Young [3 ]
Lee, Dong-Hwan [4 ]
机构
[1] Hallym Univ, Sacred Heart Hosp, Coll Med, Div Infect Dis,Dept Internal Med, Anyang 14066, South Korea
[2] Inje Univ, Haeundae Paik Hosp, Coll Med, Div Pulmonol & Crit Care Med,Dept Internal Med, Busan 48108, South Korea
[3] Hallym Univ, Coll Med, Sacred Heart Hosp, Div Hematol Oncol,Dept Internal Med, Anyang 14066, South Korea
[4] Hallym Univ, Sacred Heart Hosp, Coll Med, Dept Clin Pharmacol, Anyang 14066, South Korea
来源
ANTIBIOTICS-BASEL | 2022年 / 11卷 / 06期
基金
新加坡国家研究基金会;
关键词
vancomycin; pharmacokinetics; structural model; number of compartments; pharmacokinetic; pharmacodynamic index; AUC; MIC; probability of target attain; PERFORMANCE;
D O I
10.3390/antibiotics11060743
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
This study aimed to investigate the effect of a structural pharmacokinetic (PK) model with fewer compartments developed following sparse sampling on the PK parameter estimation and the probability of target attainment (PTA) prediction of vancomycin. Two- and three-compartment PK models of vancomycin were used for the virtual concentration-time profile simulation. Datasets with reduced blood sampling times were generated to support a model with a lesser number of compartments. Monte Carlo simulation was conducted to evaluate the PTA. For the two-compartment PK profile, the total clearance (CL) of the reduced one-compartment model showed a relative bias (RBias) and relative root mean square error (RRMSE) over 90%. For the three-compartment PK profile, the CL of the reduced one-compartment model represented the largest RBias and RRMSE, while the steady-state volume of distribution of the reduced two-compartment model represented the largest absolute RBias and RRMSE. A lesser number of compartments corresponded to a lower predicted area under the concentration-time curve of vancomycin. The estimated PK parameters and predicted PK/PD index from models built with sparse sampling designs that cannot support the PK profile can be significantly inaccurate and unprecise. This might lead to the misprediction of the PTA and selection of improper dosage regimens when clinicians prescribe antibiotics.
引用
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页数:12
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