Maksay G, Tegyey Z, Kemény V, Lukovits I, Otvös L, Pálosi E
J Med Chem. 1979 Dec;22(12):1436-43. doi: 10.1021/jm00198a002.
Esters of the centrally acting oxazepam were investigated to find quantitative correlations between the pharmacokinetics of the parent drug and in vitro biotransformation rates and physicochemical properties of its prodrugs. The 14C-labeled aliphatic and omega-phenyl-substituted esters were administered intravenously to mice. Brain levels of the esters and oxazepam were determined and the latter was fitted to a simplified exponential equation. In vitro hydrolysis rate of the esters catalyzed by the hepatic microsomal fraction was measured with a pH stat. Pharmacokinetic constants characterizing the rising part of oxazepam brain levels correlate well with the chromatographic RM values and with in vitro maximal hydrolysis rates of the esters. The hydrolysis is capacity limited in the liver. In a closely related set of aliphatic esters, oxazepam brain penetration also correlates with the steric constant (ES) of its esters.
对中枢作用的奥沙西泮酯进行了研究，以找出母体药物的药代动力学与其前体药物的体外生物转化速率和理化性质之间的定量相关性。将14C标记的脂肪族和ω-苯基取代的酯静脉注射给小鼠。测定酯和奥沙西泮的脑内水平，并将后者拟合为简化的指数方程。用pH计测量肝微粒体部分催化的酯的体外水解速率。表征奥沙西泮脑内水平上升部分的药代动力学常数与色谱RM值以及酯的体外最大水解速率密切相关。肝脏中的水解受能力限制。在一组密切相关的脂肪族酯中，奥沙西泮的脑内渗透也与其酯的空间常数（ES）相关。
