Ruelius H W
Xenobiotica. 1987 Mar;17(3):255-65. doi: 10.3109/00498258709043936.
Comparative drug disposition studies can be useful in extrapolating from animals to man provided that the criteria indicating interspecies similarity in disposition reflect similar exposure to the foreign compound. Interspecies variability, on the other hand, can often be related to physiological or biochemical differences, thereby providing a rationale for the unsuitability or limitations of a species as a model for human metabolism. Retrospective evaluation of the following examples illustrates the relevance of the indicated disposition characteristics to risk and efficacy assessment: (a) oxaprozin (route of excretion, enterohepatic circulation and exposure; plasma concentrations and efficacy prediction); (b) ciramadol (species differences in presystemic elimination and major metabolic pathway); (c) acebutolol (pharmacologically active human metabolite absent in one of the toxicology species); (d) esmolol (duration of pharmacologic effect controlled by species dependent nature of blood esterases). Stereochemical preferences in the disposition of racemic drugs often differ among species. Extrapolations from one species to another cannot be made in this situation. Pharmacokinetic parameters based on measurements of the sum of the isomers are meaningless and potentially misleading. Future improvements can come from: computer assisted predictions of metabolic pathways; increased use of human tissues; and use of animal species physiologically similar to humans, e.g. the miniature swine.
比较药物处置研究在从动物推断到人类时可能有用，前提是表明处置过程中种间相似性的标准反映了对外源化合物的相似暴露。另一方面，种间变异性通常可能与生理或生化差异有关，从而为某一物种作为人类代谢模型的不适用性或局限性提供了理论依据。对以下实例的回顾性评估说明了所指出的处置特征与风险和疗效评估的相关性：（a）奥沙普秦（排泄途径、肠肝循环和暴露；血浆浓度和疗效预测）；（b）环拉马朵（首过消除和主要代谢途径的种间差异）；（c）醋丁洛尔（一种毒理学物种中不存在具有药理活性的人体代谢物）；（d）艾司洛尔（药理作用持续时间受物种依赖性血液酯酶性质控制）。外消旋药物处置中的立体化学偏好通常在不同物种之间存在差异。在这种情况下，不能从一个物种推断到另一个物种。基于异构体总和测量的药代动力学参数没有意义，而且可能会产生误导。未来的改进可以来自：代谢途径的计算机辅助预测；更多地使用人体组织；以及使用生理上与人类相似的动物物种，例如小型猪。
