Tateishi Hiroki, Miyazu Daisuke, Kurinami Miho, Ieiri Ichiro, Hirakawa Masaaki, Watanabe Hiroyuki
Department of Pharmacy, Fukuoka Tokushukai Hospital, 4-5 Sugukita, Kasuga-shi, Fukuoka, 816-0864, Japan.
Department of Nutrition, Fukuoka Tokushukai Hospital, 4-5 Sugukita, Kasuga-shi, Fukuoka, 816-0864, Japan.
J Pharm Health Care Sci. 2021 Nov 3;7(1):39. doi: 10.1186/s40780-021-00221-y.
Bucolome is a non-steroidal anti-inflammatory drug and uricosuric agent, currently used only in Japan. It is known to induce drug interactions by inhibiting cytochrome P450 (CYP) 2C9. It is often used to enhance the anticoagulant effect of warfarin by utilizing its drug interactions. There are only a few reports on drug interactions of bucolome and the mechanism remain poorly understood.
An 81-year-old woman with a history of type 2 diabetes mellitus was taking glimepiride 2 mg/day and voglibose 0.6 mg/day. After hospitalization, the patient underwent surgical aortic valve replacement surgery (day 0). Glimepiride and voglibose were resumed on the second postoperative day (day 2), and warfarin was started to prevent thromboembolism. Since the prothrombin time-international normalized ratio on day 9 was low at 1.24, 300 mg/day of bucolome was added to enhance the effect of warfarin. A gradual decrease in blood glucose levels was observed from the day after bucolome administration was initiated. Hypoglycemia in the 56-57 mg/dL range occurred before lunch and dinner on the 6th day (day 14) of bucolome administration, due to which voglibose was discontinued. Hypoglycemia below 70 mg/dL was not observed thereafter, and the general condition of the patient was stable.
Based on the clinical course and literature review, we believe that hypoglycemia in the present case was due to a drug interaction, caused by inhibition of CYP2C9 by bucolome and competitive inhibition of CYP2C9 by warfarin, which affected the pharmacokinetics of glimepiride. The possibility of hypoglycemia due to drug interactions should be considered by physicians, when bucolome is included to enhance the effect of warfarin, in patients taking glimepiride.
布可隆是一种非甾体抗炎药和促尿酸排泄剂，目前仅在日本使用。已知它通过抑制细胞色素P450（CYP）2C9诱导药物相互作用。它常利用其药物相互作用来增强华法林的抗凝作用。关于布可隆药物相互作用的报道较少，其机制仍知之甚少。
一名81岁的2型糖尿病女性患者，正在服用格列美脲2毫克/天和伏格列波糖0.6毫克/天。住院后，患者接受了主动脉瓣置换手术（第0天）。术后第二天（第2天）恢复服用格列美脲和伏格列波糖，并开始使用华法林预防血栓栓塞。由于第9天的凝血酶原时间-国际标准化比值较低，为1.24，因此添加300毫克/天的布可隆以增强华法林的效果。从开始服用布可隆后的第二天起，观察到血糖水平逐渐下降。在服用布可隆的第6天（第14天）午餐和晚餐前出现了56 - 57毫克/分升范围的低血糖，因此停用了伏格列波糖。此后未观察到血糖低于70毫克/分升的低血糖情况，患者的一般状况稳定。
基于临床过程和文献综述，我们认为本病例中的低血糖是由于药物相互作用引起的，布可隆抑制CYP2C9以及华法林对CYP2C9的竞争性抑制影响了格列美脲的药代动力学。当在服用格列美脲的患者中加入布可隆以增强华法林效果时，医生应考虑药物相互作用导致低血糖的可能性。
