Shan Jing1, Yue Zhu2, Wenfang Liu1, Kexu Yang1, Lili Hu2, Dan Deng2, Chunyan Lu1, Yang Lin3. 1. Clinical Pharmacology Centre, Beijing Anzhen Hospital, Capital Medical University, Beijing, China. 2. Changchun Haiyue Pharmaceutical Co., Ltd., Changchun, China. 3. Clinical Pharmacology Centre, Beijing Anzhen Hospital, Capital Medical University, Beijing, China. icp@anzhengcp.com.
Abstract
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 AUCinf [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 AUCinf 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 AUCinf 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.
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 AUCinf [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 AUCinf 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 AUCinf 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.