Brode E, Poveda Velasco A, Díaz-Rubio E, Rosell Costa R, Benavides Fissure A
Knoll AG, Ludwigshafen, Germany.
Methods Find Exp Clin Pharmacol. 1992 Mar;14(2):131-40.
The pharmacokinetic behavior of mitonafide after intravenous administration (1 h infusions) to patients (118-180 mg/m2) can be described by an open three compartment body model. Mitonafide distributes quasi-instantaneously in a central distribution volume of 102 l/m2 (median) from which it equilibrates with two peripheral compartments of 106 and 258 l/m2, respectively. Its disappearance from plasma is triexponential with half-lives of 0.28, 2.0 and 26.9 h, resulting in a clearance of 69 l/h/m2. This clearance is mainly due to the biotransformation of mitonafide leading among others to amonafide, N-acetyl-amonafide, and N-desmethyl-amonafide, which build up substantial concentrations in plasma. Their quantitative importance in terms of exposures (AUC) relative to the parent compound are 86, 197 and 28%, respectively. Terminal elimination from plasma proceeds with half-lives of 34.3, 17.6 and 27.5 h.
对患者静脉注射米托萘啶（1小时输注，剂量为118 - 180mg/m²）后的药代动力学行为可用开放三室模型描述。米托萘啶在中央分布容积为102l/m²（中位数）中几乎瞬间分布，从该容积与分别为106l/m²和258l/m²的两个外周室达到平衡。其从血浆中的消除呈三指数形式，半衰期分别为0.28、2.0和26.9小时，清除率为69l/h/m²。该清除率主要归因于米托萘啶的生物转化，这一转化过程会生成氨萘啶、N - 乙酰 - 氨萘啶和N - 去甲基 - 氨萘啶等物质，这些物质在血浆中会积累到相当高的浓度。它们相对于母体化合物在暴露量（AUC）方面的定量重要性分别为86%、197%和28%。血浆中的终末消除半衰期分别为34.3、17.6和27.5小时。
