Maksay G, Tegyey Z, Otvös L
J Med Chem. 1979 Dec;22(12):1443-7. doi: 10.1021/jm00198a003.
Pharmacokinetics of a series of prodrug-type oxazepam esters were studied in mice. The effect of hydrophobicity was investigated in relation to serum binding, brain penetration, tissue storage, and excretion. Binding to mouse serum and to human serum albumin was measured by equilibrium dialysis, and the changes in binding free energy were correlated with RM values. Brain-blood partition of the esters did not change parallel with their serum binding. An indirect correlation exists between RM of the esters and oxazepam brain accrual. Brain-blood concentration ratios of oxazepam prove that hydrolysis precedes brain penetration and hydrophobicity might primarily influence the hydrolysis rate. The amount of tissue storage and total excretion rates also correlate with hydrophobicity.
在小鼠中研究了一系列前药型奥沙西泮酯的药代动力学。研究了疏水性与血清结合、脑渗透、组织储存和排泄的关系。通过平衡透析测量与小鼠血清和人血清白蛋白的结合，并将结合自由能的变化与RM值相关联。酯类的脑血分配与其血清结合并不平行变化。酯类的RM与奥沙西泮在脑中的蓄积之间存在间接相关性。奥沙西泮的脑血浓度比证明水解先于脑渗透，疏水性可能主要影响水解速率。组织储存量和总排泄率也与疏水性相关。
