Sugimoto Mitsushige, Shirai Naohito, Nishino Masafumi, Kodaira Chise, Uotani Takahiro, Sahara Shu, Ichikawa Hitomi, Kagami Takuma, Sugimoto Ken, Furuta Takahisa
First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, 431-3192, Japan,
Eur J Clin Pharmacol. 2014 Sep;70(9):1073-8. doi: 10.1007/s00228-014-1713-y. Epub 2014 Jul 6.
The aim of therapeutic regimens using proton pump inhibitors (PPIs) in patients with acid-related diseases is to potently inhibit acid secretion for the full 24 h. However, optimum treatment is still unclear because the pharmacodynamics of PPIs differ among CYP2C19 genotypes and most of the previous studies have had loss of sample power.
Using pH monitoring, we compared acid inhibition at standard dosage of omeprazole (20 mg, 50 times), lansoprazole (30 mg, 68 times), and rabeprazole (10 mg, 65 times) in Helicobacter pylori-negative healthy young Japanese volunteers.
Median pH with rabeprazole was 5.4 (3.3-7.5), which was significantly greater than with either omeprazole [4.4 (2.1-7.3)] or lansoprazole [4.8 (3.5-6.4)] (both P < 0.05). Median 24-h pH differed among the different CYP2C19 genotypes in all three PPIs. In CYP2C19 extensive metabolizers (EMs), the genotype that is refractory to PPI treatment, median pH with omeprazole, lansoprazole, and rabeprazole was 3.8 (2.1-4.4), 4.5 (3.5-5.3) and 4.8 (3.3-7.5), respectively.
Treatment with the selected PPIs at their standard dosages had difficulty maintaining acid inhibition for a full 24 h, especially in CYP2C19 EM. However, rabeprazole has the merit of less influence of CYP2C19 genotype compared with the other PPIs.
使用质子泵抑制剂（PPI）治疗酸相关性疾病患者的目的是在24小时内有效抑制胃酸分泌。然而，最佳治疗方案仍不明确，因为PPI的药效学在CYP2C19基因分型中存在差异，并且之前的大多数研究样本量不足。
我们通过pH监测，比较了奥美拉唑（20mg，50例）、兰索拉唑（30mg，68例）和雷贝拉唑（10mg，65例）标准剂量在幽门螺杆菌阴性的健康年轻日本志愿者中的抑酸效果。
雷贝拉唑治疗后的pH中位数为5.4（3.3 - 7.5），显著高于奥美拉唑[4.4（2.1 - 7.3）]或兰索拉唑[4.8（3.5 - 6.4）]（P均<0.05）。所有三种PPI在不同CYP2C19基因分型中的24小时pH中位数存在差异。在CYP2C19广泛代谢者（EMs）中，即对PPI治疗难治的基因分型，奥美拉唑、兰索拉唑和雷贝拉唑治疗后的pH中位数分别为3.8（2.1 - 4.4）、4.5（3.5 - 5.3）和4.8（3.3 - 7.5）。
所选PPI以标准剂量治疗难以维持24小时的胃酸抑制，尤其是在CYP2C19 EMs中。然而，与其他PPI相比，雷贝拉唑受CYP2C19基因分型的影响较小。
