PDF(Pubmed)
Abstract：
UNASSIGNED: Henagliflozin is an original, selective sodium-glucose cotransporter 2 (SGLT2) inhibitor. Hydrochlorothiazide (HCTZ) is a common anti-hypertensive drug. This study aimed to evaluate the potential interaction between henagliflozin and HCTZ.
UNASSIGNED: This was a single-arm, open-label, multi-dose, three-period study that was conducted in healthy Chinese volunteers. Twelve subjects were treated in three periods, period 1: 25 mg HCTZ for four days, period 2: 10 mg henagliflozin for four days and period 3: 25 mg HCTZ + 10 mg henagliflozin for four days. Blood samples and urine samples were collected before and up to 24 hours after drug administrations on day 4, day 10 and day 14. The plasma concentrations of henagliflozin and HCTZ were analyzed using LC-MS/MS. The urine samples were collected for pharmacodynamic glucose and electrolyte analyses. Tolerability was also evaluated.
UNASSIGNED: The 90% CI of the ratio of geometric means (combination: monotherapy) for AUCτ,ss of henagliflozin and HCTZ was within the bioequivalence interval of 0.80-1.25. For henagliflozin, co-administration increased Css, max by 24.32% and the 90% CI of the GMR was (108.34%, 142.65%), and the 24-hour urine volume and glucose excretion decreased by 0.43% and 19.6%, respectively. For HCTZ, co-administration decreased Css, max by 19.41% and the 90% CI of the GMR was (71.60%, 90.72%), and the 24-hour urine volume and urinary calcium, potassium, phosphorus, chloride, and sodium excretion decreased by 11.7%, 20.8%, 11.8%, 11.9%, 22.0% and 15.5%, respectively. All subjects (12/12) reported adverse events (AEs), but the majority of theses AEs were mild and no serious AEs were reported.
UNASSIGNED: Although Css,max was affected by the combination of henagliflozin and HCTZ, there was no clinically meaningful safety interaction between them. Given these results, coadministration of HCTZ should not require any adaptation of henagliflozin dosing.
UNASSIGNED: ClinicalTrials.gov NCT06083116.
UNASSIGNED: This was a single-arm, open-label, multi-dose, three-period study that was conducted in healthy Chinese volunteers. Twelve subjects were treated in three periods, period 1: 25 mg HCTZ for four days, period 2: 10 mg henagliflozin for four days and period 3: 25 mg HCTZ + 10 mg henagliflozin for four days. Blood samples and urine samples were collected before and up to 24 hours after drug administrations on day 4, day 10 and day 14. The plasma concentrations of henagliflozin and HCTZ were analyzed using LC-MS/MS. The urine samples were collected for pharmacodynamic glucose and electrolyte analyses. Tolerability was also evaluated.
UNASSIGNED: The 90% CI of the ratio of geometric means (combination: monotherapy) for AUCτ,ss of henagliflozin and HCTZ was within the bioequivalence interval of 0.80-1.25. For henagliflozin, co-administration increased Css, max by 24.32% and the 90% CI of the GMR was (108.34%, 142.65%), and the 24-hour urine volume and glucose excretion decreased by 0.43% and 19.6%, respectively. For HCTZ, co-administration decreased Css, max by 19.41% and the 90% CI of the GMR was (71.60%, 90.72%), and the 24-hour urine volume and urinary calcium, potassium, phosphorus, chloride, and sodium excretion decreased by 11.7%, 20.8%, 11.8%, 11.9%, 22.0% and 15.5%, respectively. All subjects (12/12) reported adverse events (AEs), but the majority of theses AEs were mild and no serious AEs were reported.
UNASSIGNED: Although Css,max was affected by the combination of henagliflozin and HCTZ, there was no clinically meaningful safety interaction between them. Given these results, coadministration of HCTZ should not require any adaptation of henagliflozin dosing.
UNASSIGNED: ClinicalTrials.gov NCT06083116.
摘要：
■Henagliflozin是原始的，选择性钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂。氢氯噻嗪(HCTZ)是一种常见的抗高血压药物。本研究旨在评估henagliflozin与HCTZ之间的潜在相互作用。
■这是单臂，开放标签，多剂量,在健康中国志愿者中进行的三期研究。十二个受试者在三个时期接受了治疗，第1期：25毫克HCTZ，持续4天，第2期：10mghenagliflozin4天，第3期：25mgHCTZ+10mghenagliflozin4天。在第4天、第10天和第14天,在药物施用之前和之后24小时收集血样和尿样。使用LC-MS/MS分析了henagliflozin和HCTZ的血浆浓度。收集尿样用于药效学葡萄糖和电解质分析。还评估了耐受性。
■AUCτ的几何均值（组合：单一疗法）比率的90％CI，henagliflozin和HCTZ的ss在0.80-1.25的生物等效性区间内。对于Henagliflozin来说,共同管理增加了Css，最大值为24.32%，GMR的90%CI为(108.34%，142.65%），24小时尿量和葡萄糖排泄量分别下降0.43%和19.6%,分别。对于HCTZ，共同管理减少了Css，最大值为19.41%，GMR的90%CI为(71.60%，90.72%)，24小时尿量和尿钙，钾，磷，氯化物,钠排泄减少了11.7%,20.8%,11.8%,11.9%,22.0%和15.5%，分别。所有受试者（12/12）报告不良事件（AE），但大多数这些AE是轻度的，没有严重的AE报告。
■虽然Css，max受henagliflozin和HCTZ组合的影响，它们之间没有临床意义的安全性相互作用.鉴于这些结果,HCTZ的联合给药不应该需要对henagliflozin剂量进行任何调整。
■ClinicalTrials.govNCT06083116。
■这是单臂，开放标签，多剂量,在健康中国志愿者中进行的三期研究。十二个受试者在三个时期接受了治疗，第1期：25毫克HCTZ，持续4天，第2期：10mghenagliflozin4天，第3期：25mgHCTZ+10mghenagliflozin4天。在第4天、第10天和第14天,在药物施用之前和之后24小时收集血样和尿样。使用LC-MS/MS分析了henagliflozin和HCTZ的血浆浓度。收集尿样用于药效学葡萄糖和电解质分析。还评估了耐受性。
■AUCτ的几何均值（组合：单一疗法）比率的90％CI，henagliflozin和HCTZ的ss在0.80-1.25的生物等效性区间内。对于Henagliflozin来说,共同管理增加了Css，最大值为24.32%，GMR的90%CI为(108.34%，142.65%），24小时尿量和葡萄糖排泄量分别下降0.43%和19.6%,分别。对于HCTZ，共同管理减少了Css，最大值为19.41%，GMR的90%CI为(71.60%，90.72%)，24小时尿量和尿钙，钾，磷，氯化物,钠排泄减少了11.7%,20.8%,11.8%,11.9%,22.0%和15.5%，分别。所有受试者（12/12）报告不良事件（AE），但大多数这些AE是轻度的，没有严重的AE报告。
■虽然Css，max受henagliflozin和HCTZ组合的影响，它们之间没有临床意义的安全性相互作用.鉴于这些结果,HCTZ的联合给药不应该需要对henagliflozin剂量进行任何调整。
■ClinicalTrials.govNCT06083116。
