Sánchez J L, Dominguez A R, Lane J R, Anderson P O, Capparelli E V, Cornejo-Bravo J M
Universidad Autónoma de Baja California, Facultad de Ciencias Químicas e Ingeniería,Tijuana, Mexico.
Int J Clin Pharmacol Ther. 2010 Aug;48(8):525-33. doi: 10.5414/cpp48525.
A vancomycin population pharmacokinetic prediction model for adult and elderly patients was developed using NONMEM. The predictability of the model was studied and compared with ten other models.
Data were collected from routine care of 141 subjects. NONMEM was used to derive a population model. After internal evaluation using the bootstrap technique, external validation was studied using an independent dataset that consisted of 95 subjects; a statistical comparison of precision and bias was conducted.
A two-compartment open model was derived with body weight, age, and CLcr as covariates. The bootstrap process showed stability of the model. A comparison of subjects older and younger than 65 years found that the older group had a mean clearance of 2.24 (+/- 1.2) l/h compared to 4.03 (+/- 1.7) l/h, and a peripheral volume of 43.7 (+/- 5.1) l compared to 28.4 (+/- 5.3) l compared to younger patients. These values were modeled using CLcr in the clearance equation and Vd as a function of age. The eleven models studied showed a bias in predicting serum concentrations from the test database that ranged from 0.35 mg/l to -5.93 mg/l. Precision ranged from 4.53 mg/l to 8.05 mg/l. Our method ranked in fourth place overall and when compared statistically its bias was different from the method that ranked in second place by -1.45 (95% CI -2.46, -0.42; p = 0.005), and different from all the methods that ranked worse. The only difference in precision was with the method that ranked in eleventh place with a relative precision of 0.49 (95% CI 0.27, 0.70; p < 0.001).
A two-compartment open model fitted the data with weight, age, and CLcr as covariates. The derived method ranked in fourth place overall. The two-compartment nature of two of the equations studied did not provide an advantage. A future study with more data in the distribution phase could provide a model with better predictability.
使用非线性混合效应模型（NONMEM）开发成人及老年患者的万古霉素群体药代动力学预测模型。研究该模型的预测能力，并与其他十个模型进行比较。
从141名受试者的常规护理中收集数据。使用NONMEM推导群体模型。在使用自助法进行内部评估后，使用由95名受试者组成的独立数据集进行外部验证；对精度和偏差进行统计比较。
推导得到一个二室开放模型，以体重、年龄和肌酐清除率（CLcr）作为协变量。自助法过程显示模型具有稳定性。对65岁以上和65岁以下的受试者进行比较发现，老年组的平均清除率为2.24（±1.2）l/h，而年轻患者为4.03（±1.7）l/h；老年组的外周室容积为43.7（±5.1）l，而年轻患者为28.4（±5.3）l。这些值在清除率方程中使用CLcr进行建模，并将分布容积（Vd）作为年龄的函数。所研究的11个模型在预测测试数据库中的血清浓度时显示出偏差，范围从0.35mg/l至-5.93mg/l。精度范围为4.53mg/l至8.05mg/l。我们的方法总体排名第四，在统计学比较中，其偏差与排名第二的方法相差-1.45（95%置信区间-2.46，-0.42；p=0.005），且与所有排名更差的方法不同。精度方面的唯一差异是与排名第十一位的方法，相对精度为0.49（95%置信区间0.27，0.70；p<0.001）。
一个二室开放模型以体重、年龄和CLcr作为协变量拟合数据。推导得到的方法总体排名第四。所研究的两个方程的二室性质并未提供优势。未来在分布相进行更多数据的研究可能会提供一个预测能力更好的模型。
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