Kolenda K D, Grille W, Johnsen K
Med Klin. 1979 Dec 14;74(50):1914-22.
Tolbutamide belongs to those drugs responsible for the majority of drug interactions. E.g. Tolbutamide metabolism has been shown to be inhibited by coumarole derivatives. We determined plasma-tolbutamide levels in diabetic out-patients for one year. The results obtained indicate no difference in patients additionally treated with either digoxin or digoxin and alpha-methyldopa, or buformin and phenprocumone as compared with control groups. Interactions with respect to biotransformation should not be expected as far as digoxin, alpha-Methyldopa, or buformine were concerned, since these compounds do not share a common metabolic pathway with tolbutamide. In a different group of patients the elimination half life of tolbutamide under the influence of phenprocoumone was additonally determined. Differences could not be detected. This finding can be explained by means of enzyme-kinetic considerations, since phenprocumone, in contrast to dicoumarole, becomes metabolized according to a first order reaction. Competitive enzyme inhibition with tolbutamide which is metabolized similarly to phenprocoumone, therefore appears improbable.
甲苯磺丁脲属于引发大多数药物相互作用的药物。例如,香豆素衍生物已被证明可抑制甲苯磺丁脲的代谢。我们对糖尿病门诊患者的血浆甲苯磺丁脲水平进行了为期一年的测定。所得结果表明,与对照组相比,额外接受地高辛或地高辛与α-甲基多巴联合治疗,或二甲双胍与苯丙香豆素联合治疗的患者并无差异。就地高辛、α-甲基多巴或二甲双胍而言,预计不会发生生物转化方面的相互作用,因为这些化合物与甲苯磺丁脲没有共同的代谢途径。在另一组患者中,还测定了苯丙香豆素影响下甲苯磺丁脲的消除半衰期。未检测到差异。这一发现可以通过酶动力学考量来解释,因为与双香豆素不同,苯丙香豆素按一级反应进行代谢。因此,与甲苯磺丁脲类似进行代谢的苯丙香豆素发生竞争性酶抑制的可能性似乎不大。