To the Editors:
Mucolytics, such ass-carboxymethyl-l- 半胱氨酸,在治疗慢性阻塞性气道疾病中起着作用,但它们的明显不可靠性导致了关于其实用性的分歧1-3。The failure to achieve any measurable benefit with some patients presumably reflects underlying interindividual differences within the patient cohort, and not that the drug itself is without efficacy. In this respect, one major topic affecting clinical efficacy of a drug is its disposition and fate following administration, and, in particular, those factors that influence its subsequent metabolism and deactivation.
代谢命运s-carboxymethyl-l-cysteine, an extensively used and widely available mucoactive drug, is now known to be complex. Detailed and rigorous studies in humans have revealed that the biotransformation of the drug varies widely within the same individual, with little sulphoxide (sulphur oxygenated) metabolites being produced following night-time administration4。这种看似微不足道的观察至关重要,因为最近的工作表明该药物起源于自由基清除剂5,,,,6在这方面,硫化物(母体化合物)是活性物种,具有硫化代谢物(已经氧化)不活跃。因此,夜间摄入药物应比白天给药更有益。然而,这种新陈代谢(失活)的昼夜差异被覆盖在潜在的遗传多态性上,该多态性使患者人群的传播s-carboxymethyl-l-cysteine sulphoxidation capacities7(fig. 1⇓)。那些相对有效的硫氧化剂的个体将迅速产生不活跃的氧化代谢物,而在此过程中相对缺乏的人将在更长的时间内暴露于活性硫化物中,从而有效地模仿夜间给药状况。在有效的荧光酶中,该药物的标准剂量可能几乎没有影响。这些反应的潜在酶学尚不清楚,但是两种胞质酶,半胱氨酸二氧酶和苯丙氨酸4-羟化酶已被涉及8。
显然,使用这种特殊的粘液溶液剂对治疗的“广泛笔触”方法对所有人都不适用。认识到相同剂量的s-carboxymethyl-l- 半胱氨酸对所有患者都不是同等有效的,应使该治疗方案的这一部分能够针对每个患者或亚组的患者量身定制。删除或预扣治疗是因为在某些受试者中似乎无效,对于可能获得福利的患者人群的比例显然是不正确的。在进行粘液疗法之前,某种形式的实际筛查将允许分配正确的剂量。
We would welcome correspondence concerning the efficacy, or otherwise, ofs-carboxymethyl-l- 半胱氨酸治疗慢性阻塞性肺疾病。
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