埃索美拉唑/碳酸氢钠速释胶囊在中国健康志愿者中的药代动力学和药效学：一项交叉、随机对照试验。
Pharmacokinetics and Pharmacodynamics of Esomeprazole/Sodium Bicarbonate Immediate-Release Capsules in Healthy Chinese Volunteers: A Cross-Over, Randomized Controlled Trial.
机构信息
Clinical Pharmacology Centre, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
Changchun Haiyue Pharmaceutical Co., Ltd., Changchun, China.
出版信息
Adv Ther. 2021 Mar;38(3):1660-1676. doi: 10.1007/s12325-021-01644-7. Epub 2021 Feb 11.
INTRODUCTION
Esomeprazole delayed release tablets (ESO) are one of the most effective treatments for acid-related disorders. The purpose of this study is to compare the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of an immediate-release capsule formulation containing esomeprazole 20 mg and sodium bicarbonate 1100 mg (IR-ESO) compared to those of the esomeprazole delayed release tablet 20 mg (ESO). In addition, the impact of CYP2C19 gene polymorphisms on PK and PD was evaluated.
METHODS
A single-center, open-label, randomized, 2-treatment, 2-sequence, and 2-period crossover study was conducted in 40 healthy Chinese subjects. Subjects received either IR-ESO or ESO for 5 days. After single- and multiple-dosing administration, blood samples were collected for PK analysis, and intragastric pH was assessed by 24-h pH monitoring. The CYP2C19 gene polymorphisms were analyzed by Sanger sequencing.
RESULTS
The geometric mean ratios (90% confidence interval) [GMR (95%CI)] of IR-ESO/ESO for AUC [single dose: 103.60% (96.58%, 111.14%), multiple doses: 101.65% (97.88%, 105.57%)] were within the range of 80.00-125.00%. The AUC showed an increasing trend between CYP2C19 extensive metabolizer (EM), intermediate metabolizer (IM), and poor metabolizer (PM) after single-dose and multiple-dose administration (p < 0.05). The GMR (95%CI) of IR-ESO/ESO for 24-h integrated gastric acidity from baseline [single dose: 101.07% (96.56%, 105.78%), multiple doses: 101.24% (97.74%, 104.86%)] were within the range of 80.00-125.00%. The percentage changes in 24-h integrated gastric acidity from baseline was significant difference between EM, IM, and PM after single-dose IR-ESO and ESO (p < 0.05). Drugs were all well tolerated, and there were no significant differences in adverse events between IR-ESO and ESO.
CONCLUSION
This study showed that IR-ESO can inhibit the secretion of gastric acid rapidly and continuously, and that the PK and PD of IR-ESO are affected by CYP2C19 genotypes. The GMR (95% CI) of IR-ESO/ESO for AUC and the percentage changes in 24-h integrated gastric acidity from baseline were all within the range of 80.00-125.00%.
TRIAL REGISTRATION
Chinese Clinical Trial Registry: ChiCTR1900024935.
简介
艾司奥美拉唑延迟释放片（ESO）是治疗酸相关疾病最有效的药物之一。本研究旨在比较含有埃索美拉唑 20mg 和碳酸氢钠 1100mg 的速释胶囊制剂（IR-ESO）与埃索美拉唑延迟释放片 20mg（ESO）的安全性、药代动力学（PK）和药效动力学（PD）。此外，还评估了 CYP2C19 基因多态性对 PK 和 PD 的影响。
方法
一项在中国 40 名健康受试者中进行的单中心、开放标签、随机、2 种治疗、2 种序列和 2 期交叉研究。受试者接受 IR-ESO 或 ESO 治疗 5 天。单次和多次给药后采集血样进行 PK 分析，并通过 24 小时 pH 监测评估胃内 pH 值。通过 Sanger 测序分析 CYP2C19 基因多态性。
结果
IR-ESO/ESO 的 AUC 的几何均数比值（90%置信区间）[GMR（95%CI）]（单次剂量：103.60%（96.58%，111.14%），多次剂量：101.65%（97.88%，105.57%）]在 80.00-125.00%范围内。单次和多次给药后，CYP2C19 广泛代谢者（EM）、中间代谢者（IM）和弱代谢者（PM）的 AUC 呈上升趋势（p<0.05）。IR-ESO/ESO 对 24 小时基线胃内酸度的综合影响的 GMR（95%CI）（单次剂量：101.07%（96.56%，105.78%），多次剂量：101.24%（97.74%，104.86%））在 80.00-125.00%范围内。单次 IR-ESO 和 ESO 后，EM、IM 和 PM 之间的 24 小时基线胃内酸度综合变化的百分比有显著差异（p<0.05）。
药物均耐受良好，IR-ESO 和 ESO 之间不良反应无显著差异。
结论
本研究表明，IR-ESO 可快速持续抑制胃酸分泌，IR-ESO 的 PK 和 PD 受 CYP2C19 基因型影响。IR-ESO/ESO 的 AUC 的 GMR（95%CI）和 24 小时基线胃内酸度综合变化的百分比均在 80.00-125.00%范围内。
试验注册
中国临床试验注册中心：ChiCTR1900024935。
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