Perry W, Stamp T C
Clin Pharmacol Ther. 1984 May;35(5):710-5. doi: 10.1038/clpt.1984.99.
As measured by urinary D-glucaric acid excretion, an index of hepatic enzyme induction, glutethimide was the most powerful of six such inducers tested. In patients with tuberculosis, rifampicin, 450 mg daily, induced excretion rates of the lower dose range of anticonvulsants in epileptics. The effect was detectable in the first few days but the degree and rate of rise to maximum excretion were variable. This may be due either to disposition of rifampicin or to genetic susceptibility to enzyme induction. Plasma beta-glucuronidase, an essential enzyme of the glucuronic acid pathway, could be induced independently of an increase in D-glucaric acid excretion. Plasma gamma-glutamyltranspeptidase-levels, an index of hepatic microsomal enzyme induction, were elevated in only 20 of 83 subjects receiving rifampicin and isoniazid, and in all of them urinary D-glucaric acid excretion was normal. Neither of these indices, therefore, showed hepatic enzyme induction during combined therapy when other pathways such as oxidative metabolism continued to be induced. Different active sites of rifampicin and isoniazid on glucuronic acid and other biochemical pathways emphasize the complexity of final metabolic effects in patients on long-term therapy.
以尿中D - 葡糖醛酸排泄量（一种肝酶诱导指标）衡量，格鲁米特是所测试的六种此类诱导剂中效力最强的。在结核病患者中，每日450毫克的利福平可诱导癫痫患者体内抗惊厥药低剂量范围的排泄率升高。在最初几天即可检测到这种效应，但排泄量升至最大值的程度和速率各不相同。这可能是由于利福平的处置方式，也可能是由于对酶诱导的遗传易感性。血浆β - 葡糖醛酸酶是葡糖醛酸途径的一种关键酶，其诱导可独立于D - 葡糖醛酸排泄量的增加。血浆γ - 谷氨酰转肽酶水平是肝微粒体酶诱导的一个指标，在83名接受利福平和异烟肼治疗的受试者中，只有20人的该指标升高，而且他们所有人的尿D - 葡糖醛酸排泄均正常。因此，当氧化代谢等其他途径持续被诱导时，在联合治疗期间这两个指标均未显示肝酶诱导。利福平和异烟肼在葡糖醛酸及其他生化途径上的不同活性位点，凸显了长期治疗患者最终代谢效应的复杂性。
