Stengård J H, Saarni H U, Knip M, Lahtela J T, Stenbäck F, Sotaniemi E A
Res Commun Chem Pathol Pharmacol. 1986 Nov;54(2):147-56.
The addition of phenobarbital (PB) to a sulphonylurea (SU) regimen may improve glycemic control in patients with non- insulin dependent diabetes mellitus (NIDDM, type II). Since SU reactions may be modified, we investigated glucose metabolism in rats with combined PB and SU treatment. Chlorpropamide (CHL) and glibenclamide (GB) were selected as SU drugs. The combination of PB to the CHL or GB regimens induced the drug metabolism enzymes excluding aminopyrine N-demethylase activity, which was enhanced by GB but not CHL. The CHL and GB treatments lowered blood glucose (BG) concentration and decreased hepatic glucose-6-phosphate phosphohydrolase (G6P hydrolase) activity and glycogen reserves in the rats. The concomitant administration of PB and the SUs decreased hepatic G6P hydrolase activity and glycogen content in the animals, whereas the BG level remained unaltered. The hepatic glycogen content was decreased more markedly in the CHL plus PB than in the CHL alone treated animals. The findings suggests that enzyme inducers modify the action of SU in rats. Hepatic drug and glucose metabolizing enzymes seems also to respond to distinct PB plus SU combinations in different ways.
在磺脲类药物（SU）治疗方案中添加苯巴比妥（PB）可能会改善非胰岛素依赖型糖尿病（NIDDM，II型）患者的血糖控制。由于SU的反应可能会被改变，我们研究了联合使用PB和SU治疗的大鼠的葡萄糖代谢情况。选择氯磺丙脲（CHL）和格列本脲（GB）作为SU药物。PB与CHL或GB治疗方案联合使用可诱导药物代谢酶，但不包括氨基比林N-脱甲基酶活性，GB可增强该活性，而CHL则不能。CHL和GB治疗可降低大鼠的血糖（BG）浓度，并降低肝脏葡萄糖-6-磷酸磷酸水解酶（G6P水解酶）活性和糖原储备。PB与SU同时给药可降低动物肝脏G6P水解酶活性和糖原含量，而BG水平保持不变。CHL加PB组动物肝脏糖原含量的降低比单独使用CHL治疗的动物更明显。这些发现表明，酶诱导剂可改变SU在大鼠体内的作用。肝脏药物和葡萄糖代谢酶似乎也以不同方式对不同的PB加SU组合做出反应。
