Mirfazaelian Ahmad, Kim Kyu-Bong, Lee Sookwang, Kim Hyo J, Bruckner James V, Fisher Jeffrey W
Department of Pharmaceutics, School of Pharmacy, University of Tehran, Tehran, Iran.
J Toxicol Environ Health A. 2007 Mar 1;70(5):429-38. doi: 10.1080/15287390600755265.
Growth equations can be used in physiologically based pharmacokinetic (PBPK) modeling to provide physiological parameters (e.g., body weight, tissue/organ volumes) for maturing rodents. No diligent systematic exercise was found in the literature dealing with growth equations for developing rats' tissues. A generalized Michaelis-Menten (GMM) model, originally developed to fit body weight vs. age data, was chosen to estimate different physiological compartment sizes. The GMM model has the functional form: Wt = (Wt(o).K(gamma) + Wt(max).Age(gamma))/(K(gamma) + Age(gamma)) where Wt is organ/tissue weight at a specified age, Wt(o) and Wt(max) are weight at birth and maximal growth respectively, and K and gamma are constants. Weights of freshly collected organs (liver, spleen, kidneys, heart, lungs, brain, gastrointestinal tract and adipose tissue), measured in male Sprague-Dawley rats of different ages (1-280 d) in our laboratory, were used to evaluate this model's performance. The GMM model was fitted to the organ weights, and the resulting parameters were statistically significant for all organs and tissues. Organ weights were highly correlated with their respective ages. GMM-derived organ growth and percent body weight (%BW) fractions of different tissues were plotted against animal age and compared with experimental values. The GMM-based organ growth and %BW fraction profiles were in general agreement with our empirical data as well as previous studies. The GMM model gave adequately precise weight predictions at all ages for all the tissues/organs examined.
生长方程可用于基于生理的药代动力学（PBPK）建模，以提供成熟啮齿动物的生理参数（如体重、组织/器官体积）。在有关发育中大鼠组织生长方程的文献中，未发现详尽的系统性研究。选择最初用于拟合体重与年龄数据的广义米氏（GMM）模型来估计不同生理区室的大小。GMM模型的函数形式为：Wt = (Wt(o).K(γ) + Wt(max).Age(γ))/(K(γ) + Age(γ))，其中Wt是特定年龄时的器官/组织重量，Wt(o)和Wt(max)分别是出生时的体重和最大生长体重，K和γ是常数。在我们实验室中，对不同年龄（1 - 280天）的雄性斯普拉格 - 道利大鼠新鲜采集的器官（肝脏、脾脏、肾脏、心脏、肺、脑、胃肠道和脂肪组织）重量进行测量，以评估该模型的性能。将GMM模型拟合到器官重量上，所得参数对所有器官和组织均具有统计学意义。器官重量与各自的年龄高度相关。将GMM推导的器官生长和不同组织的体重百分比（%BW）分数与动物年龄作图，并与实验值进行比较。基于GMM的器官生长和%BW分数曲线总体上与我们的经验数据以及先前的研究一致。GMM模型对所有检测的组织/器官在所有年龄都给出了足够精确的重量预测。
