Grosa G, Caputo O, Ceruti M, Biglino G
Istituto di Chimica Farmaceutica Applicata, Università di Torino, Italy.
Drug Metab Dispos. 1992 Sep-Oct;20(5):742-6.
Metabolic transformation of the mucoregulator and bronchodilator 7-(1,3-thiazolidin-2-ylmethyl)theophylline was studied in vitro with a rat liver microsomal preparation containing a NADPH-generating system. The only metabolite observed was 7-theophyllinacetaldehyde. In contrast to previous literature pointing out the chemical nature of 2-substituted thiazolidine ring cleavage, the formation of 7-theophyllinacetaldehyde was mediated by monooxygenase-dependent oxidation. Possibly an unstable sulfoxide was the first metabolic product, rapidly converted to 7-theophyllinacetaldehyde by hydrolysis. The sulfoxidation was apparently catalyzed mainly by flavin-containing monooxygenases, as selective thermal inactivation and methymazole significantly reduced the rate of formation of the metabolite. No N7-dealkylation pathway producing theophylline was detected, indicating a high regioselectivity in in vitro metabolism, due to the nucleophilicity of the sulfur atom.
使用含有NADPH生成系统的大鼠肝微粒体制剂，在体外研究了粘液调节剂和支气管扩张剂7-(1,3-噻唑烷-2-基甲基)茶碱的代谢转化。观察到的唯一代谢物是7-茶碱乙醛。与先前指出2-取代噻唑烷环裂解化学性质的文献相反，7-茶碱乙醛的形成是由单加氧酶依赖性氧化介导的。可能一种不稳定的亚砜是第一个代谢产物，通过水解迅速转化为7-茶碱乙醛。亚砜氧化显然主要由含黄素单加氧酶催化，因为选择性热失活和甲巯咪唑显著降低了代谢物的形成速率。未检测到产生茶碱的N7-脱烷基途径，这表明由于硫原子的亲核性，体外代谢具有高区域选择性。
