Stella V J, Pipkin J D
J Pharm Sci. 1976 Aug;65(8):1161-5. doi: 10.1002/jps.2600650808.
Phenylbutazone has been associated with bioavailability problems and has shown nonclassical behavior in phase-transport studies. This nonclassical behavior has been attributed, in part, to the fact that phenylbutazone, as a carbon acid, undergoes noninstantaneous ionization kinetics. Instantaneous reaction is an assumption made in many diffusion-limited transport models involving a simultaneous ionization reaction. The ionization kinetics of phenylbutazone were determined at an ionic strength of 0.1 and 25 degrees using a stopped-flow spectrophotometer. A log kobs versus pH profile for the approach to the ionization equilibrium was determined, and a mechanism consistent with the profile was postulated. The percent enol versus the diketo form of phenylbutazone acid as well as pKaenol and pKadiketo was kinetically calculated. The protonation reaction was highly catalyzed by general acids while the deprotonation reaction was highly catalyzed by general bases. The general acid, water, was a poor proton donor to the anionic form (the so-called mesomericanion) of phenylbutazone.
保泰松存在生物利用度问题，并且在相转运研究中表现出非经典行为。这种非经典行为部分归因于保泰松作为一种碳酸，其电离动力学并非瞬间完成。瞬间反应是许多涉及同时发生电离反应的扩散限制传输模型中的一个假设。使用停流分光光度计在离子强度为0.1和25℃的条件下测定了保泰松的电离动力学。确定了接近电离平衡时的log kobs对pH曲线，并推测了与该曲线一致的机制。通过动力学计算得出了保泰松酸的烯醇形式与二酮形式的百分比以及烯醇pKa和二酮pKa。质子化反应受到广义酸的高度催化，而去质子化反应受到广义碱的高度催化。广义酸水是保泰松阴离子形式（所谓的中介阴离子）的不良质子供体。
