Allen L M, Creaven P J
Clin Pharmacol Ther. 1975 Apr;17(4):492-8. doi: 10.1002/cpt1975174492.
A multicompartment pharmacokinetic model for ifosfamide has been employed using a system of first-order differential equations, which includes a term for metabolism according to Michaelis-Menten kinetics in order to describe the distribution and elimination parameters of ifosfamide in man. The model satisfactorily accounts for all the administered drug. The pseudometabolic rate constant for ifosfamide in man is found to be less than 20 percent of that reported for cyclophosphamide in man, in agreement with the more extensive metabolism of cyclophosphamide than ifosfamide. A number of the pharmacokinetic parameters for ifosfamide differ substantially from those reported for cyclophosphamide. The volume of distribution for ifosfamide metabolites was found to be approximately equal to the plasma space volume. The central compartment volume for intact ifosfamide is slightly larger than for cyclophosphamide and includes the easily diffusible extravascular space of the body and suggests lack of protein binding. The renal clearance of ifosfamide is low and about twice that of cyclophosphamide. The model indicates that only a small fraction of the total metabolites distribute into the peripheral compartment and suggests that multiple doses of the drug may be useful.
已采用一个多房室药代动力学模型来描述异环磷酰胺在人体内的分布和消除参数，该模型使用一阶微分方程组，其中包括一个根据米氏动力学的代谢项，以说明异环磷酰胺在人体内的分布和消除参数。该模型能令人满意地解释所有给药药物的情况。结果发现，异环磷酰胺在人体内的假代谢速率常数不到环磷酰胺在人体内报道值的20%，这与环磷酰胺比异环磷酰胺有更广泛的代谢情况一致。异环磷酰胺的一些药代动力学参数与环磷酰胺报道的参数有很大差异。异环磷酰胺代谢物的分布容积约等于血浆空间容积。完整异环磷酰胺的中央房室容积略大于环磷酰胺，包括身体易扩散的血管外空间，提示缺乏蛋白质结合。异环磷酰胺的肾清除率较低，约为环磷酰胺的两倍。该模型表明，总代谢物中只有一小部分分布到周边房室，提示多次给药可能有效。
