Hutchaleelaha A, Chow H H, Mayersohn M
Department of Pharmacy Practice and Science, College of Pharmacy, University of Arizona, Tucson 85721, USA.
J Pharm Pharmacol. 1997 Feb;49(2):178-83. doi: 10.1111/j.2042-7158.1997.tb06775.x.
This study employed several interspecies scaling methods, to evaluate the applicability of extrapolating to man, pharmacokinetic information obtained from animals for amphotericin B, an anti-fungal drug. Pharmacokinetic parameters from four animal species (mouse, rat, monkey and dog) and man were obtained from the literature or from analysis of data reported in the literature. The allometric relationships (obtained from four animal species) as a function of species body weight (W; kg) for systemic clearance per maximum life span potential (CLS/MLP), steady-state volume of distribution (VSS), apparent volume of distribution (V beta) and volume of the central compartment (VC) were: 5691W1.096; 2.46W0.839; 3.08W0.948 and 1.07W0.965, respectively. The allometric relationships for half-life (h) and mean residence time (h) did not scale well with body weight. The prediction of pharmacokinetic parameters in man from the allometric equations do not always agree with those reported in the literature which are based upon a limited number of studies with few human subjects. The plasma concentration-time profiles from these animals were adjusted by normalizing the concentration with dose/W0.948, and re-plotted on different pharmacokinetic time scales. The syndesichrons plot produced an almost superimposable profile of adjusted concentrations as a function of adjusted time among the four species.
本研究采用了几种种间缩放方法，以评估将从动物获得的抗真菌药物两性霉素B的药代动力学信息外推至人类的适用性。四种动物物种（小鼠、大鼠、猴和狗）以及人类的药代动力学参数是从文献中获取的，或通过对文献报道的数据进行分析得到的。每最大寿命潜力的全身清除率（CLS/MLP）、稳态分布容积（VSS）、表观分布容积（Vβ）和中央室容积（VC）作为物种体重（W；kg）的函数的异速生长关系（从四种动物物种获得）分别为：5691W1.096；2.46W0.839；3.08W0.948和1.07W0.965。半衰期（h）和平均驻留时间（h）的异速生长关系与体重的缩放效果不佳。根据异速生长方程对人类药代动力学参数的预测并不总是与文献中报道的结果一致，文献中的结果基于对少数人类受试者的有限研究。通过用剂量/W0.948对浓度进行归一化来调整这些动物的血浆浓度-时间曲线，并在不同的药代动力学时间尺度上重新绘制。同步图产生了四种物种中调整浓度作为调整时间的函数的几乎可叠加的曲线。
