Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Finland.
J Intern Med. 2010 Oct;268(4):359-66. doi: 10.1111/j.1365-2796.2010.02257.x.
Sulphonylureas are widely used in the treatment of type 2 diabetes mellitus (T2DM). Based on laboratory findings, we determined the clinical significance of potential CYP2C9-mediated drug-drug interactions in hospitalized patients receiving glibenclamide, glimepiride or glipizide, all of which are metabolized by CYP2C9, together with a CYP2C9 inhibitor.
DESIGN, SETTING AND SUBJECTS: An observational pharmaco-epidemiological database study was performed in a university hospital setting with 3884 patients with T2DM.
Efficacy and safety of sulphonylurea therapy during the potential interaction (sulphonylurea treatment with a CYP2C9 inhibitor) vs. control periods (sulphonylurea treatment without a CYP2C9 inhibitor) were estimated using laboratory parameters.
Almost 20% of patients were exposed to a potential drug-drug interaction with a CYP2C9 inhibitor during sulphonylurea treatment. More than 75% of the potential interactions occurred with trimethoprim, metronidazole and fluconazole. When all sulphonylureas were pooled and adjusted for age, gender, ward and sulphonylurea dose, mean and maximum fasting plasma glucose concentrations as well as maximum values of glycosylated haemoglobin were significantly lower during the interaction periods compared with control periods, whereas mean and minimum activities of alanine amino transferase and gamma-glutamyl transferase were higher. The minimum fasting plasma glucose values were more often below the target range in patients with potential interactions. The sulphonylurea dose did not differ significantly between patients who were or were not concomitantly treated with a potentially interacting drug.
Concomitant use of a CYP2C9 inhibitor results in exaggerated pharmacodynamic effects of sulphonylureas and increases the risk of hypoglycaemia in T2DM patients receiving glibenclamide, glimepiride or glipizide.
磺酰脲类药物被广泛用于治疗 2 型糖尿病（T2DM）。基于实验室研究结果，我们确定了同时接受 CYP2C9 抑制剂治疗的住院 T2DM 患者中，潜在的 CYP2C9 介导的药物相互作用的临床意义，这些患者正在接受格列本脲、格列美脲或格列吡嗪治疗，而这三种药物均由 CYP2C9 代谢。
设计、地点和研究对象：在一家大学医院进行了一项观察性药物流行病学数据库研究，纳入了 3884 名 T2DM 患者。
使用实验室参数来评估磺酰脲类药物治疗期间（磺酰脲类药物与 CYP2C9 抑制剂合用）与对照期间（磺酰脲类药物无 CYP2C9 抑制剂合用）的疗效和安全性。
近 20%的患者在磺酰脲类药物治疗期间暴露于潜在的 CYP2C9 抑制剂药物相互作用中。超过 75%的潜在相互作用发生在与甲氧苄啶、甲硝唑和氟康唑的合用中。当所有磺酰脲类药物汇总，并根据年龄、性别、病房和磺酰脲类药物剂量进行调整后，与对照期相比，交互期的平均和最大空腹血糖浓度以及糖化血红蛋白的最大值显著降低，而丙氨酸氨基转移酶和γ-谷氨酰转移酶的平均和最小活性升高。在潜在相互作用的患者中，最低空腹血糖值更常低于目标范围。接受潜在相互作用药物治疗的患者与未接受治疗的患者的磺酰脲类药物剂量无显著差异。
同时使用 CYP2C9 抑制剂会导致磺酰脲类药物的药效学作用增强，并增加接受格列本脲、格列美脲或格列吡嗪治疗的 T2DM 患者发生低血糖的风险。
