Actis Giovanni-C, Pellicano Rinaldo, Rizzetto Mario, Ayoubi Muhammad, Leone Nicola, Tappero Gianfranco, Pazienza Paola, Rosina Floriano
Division of Gastro-Hepatology, Ospedale Gradenigo, Corso Regina 10, Torino 10153, Italy.
World J Gastroenterol. 2009 Mar 28;15(12):1420-6. doi: 10.3748/wjg.15.1420.
Data from both basic research and clinical experience continue to suggest that mesalamines and thiopurines are effective and efficient for the maintenance of remission of inflammatory bowel diseases. Several decades following the formalization of their indications, attention on these two drugs has been fostered by recent achievements. Demonstration of the ability of mesalamine to activate a colonocyte differentiation factor has shed light on its chemopreventive effects on colorectal cancer; in addition to their anti-proliferative efficacy, thiopurines have been shown to be specific regulators of apoptosis. The two drugs are often co-administered in clinical practice. Recent advancements have shown that mesalamines exert a positive synergism in this context, insofar as they can inhibit side-methylation of thiopurines and hasten the function of the main immunosuppressive pathways. Considering that up to 40% of patients cannot tolerate thiopurines, such renovated targets have stimulated efforts to improve compliance by research on the toxicity mechanisms. The definition of genetic polymorphisms in the enzymes of thiopurine metabolism, and the uncovering of synergistic drug interactions, such as that with allopurinol, are just two of the results of such efforts. Interaction between basic research and clinical practice has continued to inform indications and refine the prescriptions of mesalamines and thiopurines; these have not been restrained (they have been implemented in some cases) by the advent of the novel biological molecules with anti-cytokine activity.
基础研究和临床经验的数据均持续表明,美沙拉嗪和硫唑嘌呤对维持炎症性肠病的缓解有效且高效。在其适应证正式确定数十年后,近期的研究成果进一步推动了对这两种药物的关注。美沙拉嗪激活结肠细胞分化因子能力的证实,揭示了其对结直肠癌的化学预防作用;除了抗增殖功效外,硫唑嘌呤还被证明是细胞凋亡的特异性调节剂。在临床实践中,这两种药物常联合使用。近期的进展表明,在这种情况下美沙拉嗪发挥了积极的协同作用,因为它们可以抑制硫唑嘌呤的侧甲基化并加速主要免疫抑制途径的功能。鉴于高达40%的患者无法耐受硫唑嘌呤,这些新的靶点促使人们通过研究毒性机制来提高用药依从性。硫唑嘌呤代谢酶基因多态性的定义以及协同药物相互作用(如与别嘌呤醇的相互作用)的发现,只是这些努力的部分成果。基础研究与临床实践之间的相互作用持续为美沙拉嗪和硫唑嘌呤的适应证及用药方案提供依据;这些并未因具有抗细胞因子活性的新型生物分子的出现而受到限制(在某些情况下已得到应用)。