Janssen Research & Development, LLC, Raritan, NJ, USA.
Janssen Research & Development, A Division of Janssen Pharmaceutica NV, Beerse, Belgium.
Clin Pharmacol Drug Dev. 2015 May-Jun;4(3):226-36. doi: 10.1002/cpdd.166. Epub 2014 Oct 27.
Drug-drug interactions between canagliflozin, a sodium glucose co-transporter 2 inhibitor, and glyburide, metformin, and simvastatin were evaluated in three phase-1 studies in healthy participants. In these open-label, fixed sequence studies, participants received: Study 1-glyburide 1.25 mg/day (Day 1), canagliflozin 200 mg/day (Days 4-8), canagliflozin with glyburide (Day 9); Study 2-metformin 2,000 mg/day (Day 1), canagliflozin 300 mg/day (Days 4-7), metformin with canagliflozin (Day 8); Study 3-simvastatin 40 mg/day (Day 1), canagliflozin 300 mg/day (Days 2-6), simvastatin with canagliflozin (Day 7). Pharmacokinetic parameters were assessed at prespecified intervals. Co-administration of canagliflozin and glyburide did not affect the overall exposure (maximum plasma concentration [Cmax ] and area under the plasma concentration-time curve [AUC]) of glyburide and its metabolites (4-trans-hydroxy-glyburide and 3-cis-hydroxy-glyburide). Canagliflozin did not affect the peak concentration of metformin; however, AUC increased by 20%. Though Cmax and AUC were slightly increased for simvastatin (9% and 12%) and simvastatin acid (26% and 18%) following coadministration with canagliflozin, compared with simvastatin administration alone; however, no effect on active 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase inhibitory activity was observed. There were no serious adverse events or hypoglycemic episodes. No drug-drug interactions were observed between canagliflozin and glyburide, metformin, or simvastatin. All treatments were well-tolerated in healthy participants.
在三项健康参与者的 I 期研究中评估了钠-葡萄糖共转运蛋白 2 抑制剂卡格列净与格列美脲、二甲双胍和辛伐他汀之间的药物相互作用。在这些开放标签、固定序列研究中，参与者接受了以下治疗：研究 1-格列美脲 1.25mg/天（第 1 天），卡格列净 200mg/天（第 4-8 天），卡格列净联合格列美脲（第 9 天）；研究 2-二甲双胍 2000mg/天（第 1 天），卡格列净 300mg/天（第 4-7 天），卡格列净联合二甲双胍（第 8 天）；研究 3-辛伐他汀 40mg/天（第 1 天），卡格列净 300mg/天（第 2-6 天），辛伐他汀联合卡格列净（第 7 天）。在预定的时间间隔评估了药代动力学参数。卡格列净与格列美脲联合用药不影响格列美脲及其代谢物（4-反式-羟基格列美脲和 3-顺式-羟基格列美脲）的总体暴露（最大血浆浓度 [Cmax] 和血浆浓度-时间曲线下面积 [AUC]）。卡格列净不影响二甲双胍的峰浓度；然而，AUC 增加了 20%。虽然与单独使用辛伐他汀相比，卡格列净联合辛伐他汀给药后辛伐他汀（9%和 12%）和辛伐他汀酸（26%和 18%）的 Cmax 和 AUC 略有增加；但是，观察到对活性 3-羟基-3-甲基-戊二酰辅酶 A（HMG-CoA）还原酶抑制活性没有影响。没有严重不良事件或低血糖发作。卡格列净与格列美脲、二甲双胍或辛伐他汀之间未观察到药物相互作用。所有治疗在健康参与者中均耐受良好。
