Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China.
Union Jiangnan Hospital, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China.
Sci Rep. 2023 Jan 20;13(1):1113. doi: 10.1038/s41598-022-27286-5.
Omeprazole and sodium bicarbonate dry suspension are effective treatments for acid-related disorders. This study compared the bioequivalence and safety of the two formulations of omeprazole and sodium bicarbonate powder and assessed how CYP2C19 gene polymorphisms affect pharmacokinetics (PK). A single-center, randomized, single-dose, 2-sequence and 2-period crossover method was performed in forty healthy Chinese subjects. Blood samples were collected after a single dose for PK (AUC, AUC, and C) analysis. The concentrations of Omeprazole in human plasma were determined by HPLC-MS/MS. Besides, the gene polymorphisms of CYP2C19 were assessed by Sanger sequencing. The geometric mean ratios (90% confidence interval) [GMR (95% CI)] of Test/Reference preparation for C: 95.2% (88.48%, 102.43%), AUC: 97.47% (94.4%, 101.02%), AUC: 97.68% (94.27%, 101.21%) were within the range of 80.00-125.00%. The non-parametric test showed no statistical difference in T between the two groups (p > 0.05). All drugs were well tolerated, no severe adverse reactions occurred, and no significant differences in adverse events between the two drugs. For CYP2C19 gene polymorphisms, the results showed that of 40 subjects, 12 subjects were extensive metabolizers, 24 were intermediate metabolizers, and 4 were poor metabolizers, the frequency of metabolic genotypes were 30%, 60%, and 10%. And the allele distributions for CYP2C19 were *1, *2, and *3 at 60%, 38.75%, and 1.25%. Both the CYP2C19 alleles and metabolic genotypes were consistent with other studies in Chinese. The results of PK parameters showed that different genotypes of CYP2C19 lead to significant differences in t, AUC, AUC and C, but no significant differences in T in each group. At the same time, we confirmed that the PK parameters of the test and reference had no differences between the males and females. This study has shown that the pharmacokinetic parameters of the two formulations are not significantly different, which showed bioequivalence and exemplary safety. CYP2C19 gene polymorphism significantly differed in the PK parameters of omeprazole sodium bicarbonate powder.
奥美拉唑和碳酸氢钠干混悬剂是治疗酸相关疾病的有效药物。本研究比较了奥美拉唑和碳酸氢钠干混悬剂两种制剂的生物等效性和安全性，并评估了细胞色素 P450 2C19（CYP2C19）基因多态性对药代动力学（PK）的影响。采用单中心、随机、单剂量、2 序列和 2 周期交叉方法，对 40 名健康中国受试者进行研究。单次给药后进行 PK（AUC、AUC 和 C）分析，采集血样。采用高效液相色谱-串联质谱法（HPLC-MS/MS）测定人血浆中奥美拉唑的浓度。此外，采用 Sanger 测序法评估 CYP2C19 基因多态性。C 的试验/参比制剂的几何均数比值（90%置信区间）[GMR（95%CI）]分别为 95.2%（88.48%，102.43%）、AUC 为 97.47%（94.4%，101.02%）、AUC 为 97.68%（94.27%，101.21%），均在 80.00-125.00%范围内。非参数检验结果显示，两组间 T 无统计学差异（p>0.05）。两种药物均耐受良好，未发生严重不良反应，两种药物的不良事件发生率无统计学差异。对于 CYP2C19 基因多态性，结果显示 40 名受试者中，12 名受试者为广泛代谢者，24 名受试者为中间代谢者，4 名受试者为弱代谢者，代谢基因型频率分别为 30%、60%和 10%。CYP2C19 的等位基因分布分别为*1、2 和3，频率分别为 60%、38.75%和 1.25%。CYP2C19 等位基因和代谢基因型在中国人中的分布与其他研究一致。PK 参数结果表明，不同 CYP2C19 基因型导致 t、AUC、AUC 和 C 有显著差异，但各组 T 无显著差异。同时，我们证实了试验和参考制剂的 PK 参数在男性和女性之间没有差异。本研究表明，两种制剂的药代动力学参数无显著差异，表现出生物等效性和良好的安全性。CYP2C19 基因多态性显著影响奥美拉唑钠碳酸氢盐干混悬剂的 PK 参数。
