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首页> 外文期刊>Journal of pharmacokinetics and biopharmaceutics >Population pharmacokinetic analysis of mizolastine and validation from sparse data on patients using the nonparametric maximum likelihood method.
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Population pharmacokinetic analysis of mizolastine and validation from sparse data on patients using the nonparametric maximum likelihood method.

机译：使用非参数最大似然方法对咪唑斯汀进行人群药代动力学分析并根据患者稀疏数据进行验证。

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摘要

A population analysis of the kinetics of mizolastine was performed from concentrations on 449 allergic patients, using the nonparametric maximum likelihood method (NPML). A two-compartment open model with zero-order absorption was used to describe the kinetics of mizolastine after oral administration. A heteroscedastic variance model was assumed for the error. To explain the kinetic variability, eight covariates were introduced in the analysis: gender, pharmaceutical dosage form, age, body weight, serum creatinine concentration, creatinine renal clearance, plasma levels of hepatic transaminases ASAT and ALAT. Their relationships to the kinetic parameters were studied by means of the estimated distribution of each kinetic parameter conditional on different levels of each covariate. An important interindividual kinetic variability was found for all parameters. Moreover, several kinetic parameters among which the duration of absorption were found to be influenced by pharmaceutical dosage form and gender. Body weight and creatinine renal clearance were found to have a little influence on the oral clearance and the smallest disposition rate constant. This population analysis was validated on a separate group of 247 other patients. For each observed concentration of this sample, a predictive distribution was computed using the individual covariates. Predicted concentrations and standardized prediction errors were deduced. The mean and variance of the standardized prediction errors were, respectively, 0.21 and 2.79. Moreover, in the validation sample, the predicted cumulative distribution function of each observed concentration was computed. Empirical distribution of these values was not significantly different from a uniform distribution, as expected under the assumption that the population model estimated by NPML is adequate.
机译：使用非参数最大似然方法（NPML）对449名过敏性患者的浓度进行了咪唑斯汀动力学的总体分析。具有零级吸收的两室开放模型用于描述口服给药后咪唑斯汀的动力学。假定该误差为异方差方差模型。为了解释动力学变异性，在分析中引入了八个协变量：性别，药物剂型，年龄，体重，血清肌酐浓度，肌酐肾清除率，肝转氨酶ASAT和ALAT的血浆水平。通过在每个协变量的不同水平上确定的每个动力学参数的估计分布，研究了它们与动力学参数的关系。发现所有参数的重要个体间动力学变异性。此外，发现吸收动力学持续时间的几个动力学参数受药物剂型和性别的影响。体重和肌酐肾清除率对口腔清除率的影响很小，并且处置速率常数最小。该人口分析已在另外247名其他患者的单独组中得到验证。对于每个观察到的该样品浓度，使用各个协变量计算预测分布。推导了预测浓度和标准预测误差。标准化预测误差的均值和方差分别为0.21和2.79。此外，在验证样本中，计算了每个观察到的浓度的预测累积分布函数。在NPML估计的人口模型足够的假设下，这些值的经验分布与均匀分布没有显着差异。

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