Office of Blood Review & Research (OBRR), Center for Biologic Evaluation and Research, Food and Drug Administration, Rockville, MD 20862, USA.
Clin Pharmacokinet. 2012 Aug 1;51(8):527-42. doi: 10.2165/11631630-000000000-00000.
The principles of allometry can be applied within a given species (intra-species scaling), for example extrapolation of pharmacokinetic parameters from adults to adolescents and older children (>5 years of age). Similarly, allometric scaling may also be used to predict pharmacokinetic parameters from normal weight subjects to the obese. The objective of this investigation was to evaluate the predictive performance of several allometric methods for the prediction of drug clearance (CL) and volume of distribution (V(d)) in the obese from normal weight subjects.
CL and V(d) values for 12 drugs for obese and normal weight subjects were obtained from the literature. Three methods (simple allometry and fixed exponents of 0.75 and 1.0) and two methods (simple allometry and a fixed exponent of 1.0) were used to predict CL and V(d), respectively, using total body weight in the obese from normal weight subjects. When data were available, ideal body weight, percentage ideal body weight and body mass index were also used for prediction purposes.
The results of the study indicated that CL could be predicted with accuracy in the obese from normal weight subjects using total body weight and simple allometry as well as fixed exponent of 0.75. The prediction of V(d) in the obese from normal weight subjects was less accurate than the prediction of CL in this population. For the prediction of CL and V(d) in the obese, simple allometry performed better than the fixed exponent of 0.75 or 1.0, respectively.
The study indicated that allometric scaling can be applied to predict CL in the obese from normal weight subjects with high accuracy. The predicted CL can then be used to select a dose to initiate a clinical trial (pharmacokinetics, safety and efficacy).
可以在特定物种内（种内比例）应用生长律原则，例如从成人外推到青少年和大龄儿童（>5 岁）的药代动力学参数。同样，也可以使用生长律比例法来预测从正常体重受试者到肥胖受试者的药代动力学参数。本研究的目的是评估几种生长律方法在从正常体重受试者预测肥胖受试者药物清除率（CL）和分布容积（V(d)）方面的预测性能。
从文献中获得了 12 种药物在肥胖和正常体重受试者中的 CL 和 V(d)值。使用三种方法（简单生长律和固定指数 0.75 和 1.0）和两种方法（简单生长律和固定指数 1.0），分别使用肥胖受试者的总体重从正常体重受试者中预测 CL 和 V(d)。当数据可用时，还使用理想体重、理想体重的百分比和体重指数进行预测。
研究结果表明，使用总体重和简单生长律以及固定指数 0.75 可以准确地从正常体重受试者预测肥胖受试者的 CL。与 CL 相比，肥胖受试者的 V(d)预测准确性较低。对于肥胖受试者 CL 和 V(d)的预测，简单生长律优于固定指数 0.75 或 1.0。
研究表明，生长律比例法可以高精度地应用于从正常体重受试者预测肥胖受试者的 CL。然后可以使用预测的 CL 来选择剂量以启动临床试验（药代动力学、安全性和疗效）。
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