Chang S C, Lee V H
Curr Eye Res. 1982;2(10):651-6. doi: 10.3109/02713688209019993.
In designing ester prodrugs to improve corneal drug bioavailability, it is important to consider the influence of chain length on both corneal permeation and hydrolysis of the prodrug. However, the second factor has received relatively little attention. The purpose of this study was to evaluate whether the ocular hydrolysis of a homologous series of alpha- and beta-naphthyl esters was influenced by chain length. Solutions of each ester were incubated with selected ocular tissues and fluids of adult albino rabbits. For the alpha-series peak hydrolytic rate was reached at the caproate (C6) ester, coinciding with minimization in the value of the Michaelis-Menten constant (Km) and maximization in the value of maximum velocity (Vmax). For the beta-series peak hydrolytic rate was reached at the valerate (C5) ester. In contrast to the alpha-series this was primarily due to a large increase in value for Km. These findings indicate that the rate of ocular esterase-mediated hydrolysis varies within a homologous series of esters, and that this chain length dependency is influenced by the chemical nature of the parent compound.
在设计酯类前药以提高角膜药物生物利用度时，考虑链长对前药角膜渗透和水解的影响非常重要。然而，第二个因素受到的关注相对较少。本研究的目的是评估一系列α-和β-萘酯的眼部水解是否受链长影响。将每种酯的溶液与成年白化兔的选定眼部组织和液体一起孵育。对于α-系列，己酸酯（C6）酯达到了最高水解速率，这与米氏常数（Km）值最小化和最大速度（Vmax）值最大化相一致。对于β-系列，戊酸酯（C5）酯达到了最高水解速率。与α-系列不同，这主要是由于Km值大幅增加。这些发现表明，眼部酯酶介导的水解速率在一系列同源酯中有所不同，并且这种链长依赖性受母体化合物化学性质的影响。
