Maafi Mounir, Maafi Wassila
Leicester School of Pharmacy, De Montfort University, The Gateway, Leicester LE1 9BH, UK.
Photochem Photobiol Sci. 2015 May;14(5):982-94. doi: 10.1039/c5pp00022j.
Despite the numerous concerns that have been raised in relation to considering 0(th), 1(st) and 2(nd)-order kinetic treatments for photodegradation characterisation and assessment of drugs, they still are employed, as they are the only tools available for these types of studies. The recently developed Φ-order kinetic models have opened new perspectives in the treatment of photoreaction kinetics and stand as the best known alternative to the classical approach. The Φ-order kinetics have been applied here to Fluvoxamine (Fluvo) with the aim of setting out a detailed and comprehensive procedure capable of rationalising photodegradation/photostability of drugs and proposing a platform for photosafety studies. Our results prove that quantum yields of drugs (0.0016 < Φ(λirr)(Fluvo) < 0.43) should a priori be considered wavelength-dependent; their photostabilisation (up to 75% for Fluvo) by means of absorption competitors can explicitly be related to a decrease of the photokinetic factor, and photoreversible drugs can be developed into efficient actinometers (as Fluvoxamine in the 260-290 nm range). A pseudo-rate-constant factor was proposed as a descriptive parameter, circumventing the limitations of overall rate-constants and allowing a comparison between kinetic data of drugs obtained under different conditions.
尽管在考虑将零级、一级和二级动力学处理用于药物光降解表征和评估方面引发了诸多担忧，但它们仍被采用，因为它们是此类研究仅有的可用工具。最近开发的 Φ 级动力学模型为光反应动力学的处理开辟了新视角，是经典方法最知名的替代方法。本文将 Φ 级动力学应用于氟伏沙明（Fluvo），目的是制定一个详细且全面的程序，能够使药物的光降解/光稳定性合理化，并为光安全性研究提供一个平台。我们的结果证明，药物的量子产率（0.0016 < Φ(λirr)(Fluvo) < 0.43）应先验地被视为与波长相关；通过吸收竞争剂实现的光稳定化（氟伏沙明可达 75%）可明确与光动力学因子的降低相关，并且光可逆药物可开发成高效的光量计（如 260 - 290 nm 范围内的氟伏沙明）。提出了一个伪速率常数因子作为描述参数，规避了总速率常数的局限性，并允许对在不同条件下获得的药物动力学数据进行比较。
