Sheiner L B
Drug Metab Rev. 1984;15(1-2):153-71. doi: 10.3109/03602538409015063.
Population pharmacokinetics describe the typical relationships between physiology (both normal and disease altered) and pharmacokinetics, the interindividual variability in these relationships, and their residual intraindividual variability. Knowledge of population kinetics can help one to choose initial drug dosage, to modify dosage appropriately in response to observed drug levels, to make rational decisions regarding certain aspects of drug regulation, and to investigate and elucidate certain research questions in pharmacokinetics. Experimental data from which population kinetics might be estimated often come from only those few individuals both willing and available to be studied. Clinical data from patients undergoing care might be more representative. These data, however, are marked by varying quality, accuracy, and precision, as well as there being few data per patient. Population pharmacokinetic parameters have traditionally been estimated either by fitting all individuals' data together as though there were no individual kinetic differences [the naive pooled data (NPD) approach], or by fitting each individual's data separately and then combining the individual parameter estimates [the two-stage (TS) approach]. These methods have certain theoretical problems which can only be aggravated when the deficiencies of data typical of clinical data are present. In this paper, the standard approaches are discussed and illustrated (using nondeficient data) in order to introduce subsequent papers in which alternative data analysis methods for population parameter estimation are defined, discussed, and compared.
群体药代动力学描述了生理学（正常和疾病状态下改变的）与药代动力学之间的典型关系、这些关系中的个体间变异性以及它们剩余的个体内变异性。群体动力学知识有助于人们选择初始药物剂量，根据观察到的药物水平适当调整剂量，就药物监管的某些方面做出合理决策，并研究和阐明药代动力学中的某些研究问题。用于估计群体动力学的实验数据通常仅来自少数愿意且能够参与研究的个体。接受治疗的患者的临床数据可能更具代表性。然而，这些数据存在质量、准确性和精密度各不相同的问题，而且每个患者的数据量很少。传统上，群体药代动力学参数的估计方法要么是将所有个体的数据拟合在一起，就好像不存在个体动力学差异一样（即单纯合并数据（NPD）方法），要么是分别拟合每个个体的数据，然后合并个体参数估计值（即两阶段（TS）方法）。这些方法存在某些理论问题，而当存在临床数据典型的不足之处时，这些问题只会更加严重。本文将讨论并举例说明（使用无缺陷数据）这些标准方法，以便引入后续文章，其中将定义、讨论和比较用于群体参数估计的替代数据分析方法。
