Nuki Y, Umeno J, Washio E, Maehata Y, Hirano A, Miyazaki M, Kobayashi H, Kitazono T, Matsumoto T, Esaki M
Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Division of Gastroenterology, International University of Health and Welfare Fukuoka Sanno Hospital, Fukuoka, Japan.
Aliment Pharmacol Ther. 2017 Aug;46(3):331-336. doi: 10.1111/apt.14134. Epub 2017 May 8.
Simultaneous use of proton pump inhibitors (PPIs) has been shown to increase the risk of nonsteroidal anti-inflammatory drug (NSAID)-induced small bowel injury.
To investigate whether polymorphisms of the cytochrome P450 2C19 gene (CYP2C19), encoding a key metabolising enzyme for PPIs, are associated with small bowel injury induced by celecoxib in combination with the PPI rabeprazole.
Study participants included 55 healthy Japanese volunteers, who participated in the PPI-NSAID Kyushu University Study using video capsule endoscopy. For 2 weeks, 26 subjects were treated with celecoxib plus rabeprazole (rabeprazole group), and 29 subjects received celecoxib plus placebo (placebo group). All subjects were genotyped for CYP2C19 using real-time fluorescent polymerase chain reaction. Subjects were sub-classified as poor metabolizers or extensive metabolizers. The incidence and number of small bowel injuries were compared between poor metabolizers and extensive metabolizers in each group.
In the rabeprazole group, the incidence of small bowel injuries was significantly higher in poor metabolizers than in extensive metabolizers (85.7% vs 31.6%, P=.026). The number of mucosal injuries in the rabeprazole group was also significantly higher in poor metabolizers compared with extensive metabolizers (median [range] 3 [0-31] vs 0 [0-7], P=.01). In addition, we found a significant interaction between CYP2C19 genotype and concomitant use of rabeprazole in subjects at risk for celecoxib-induced small bowel injury.
The CYP2C19 genotype might be associated with the risk of small bowel injury when celecoxib is combined with rabeprazole.
已表明同时使用质子泵抑制剂（PPI）会增加非甾体抗炎药（NSAID）引起的小肠损伤风险。
研究编码PPI关键代谢酶的细胞色素P450 2C19基因（CYP2C19）多态性是否与塞来昔布联合PPI雷贝拉唑引起的小肠损伤相关。
研究参与者包括55名健康的日本志愿者，他们使用视频胶囊内镜参与了PPI-NSAID九州大学研究。在2周内，26名受试者接受塞来昔布加雷贝拉唑治疗（雷贝拉唑组），29名受试者接受塞来昔布加安慰剂治疗（安慰剂组）。使用实时荧光聚合酶链反应对所有受试者进行CYP2C19基因分型。受试者被分为慢代谢型或快代谢型。比较每组中慢代谢型和快代谢型受试者小肠损伤的发生率和数量。
在雷贝拉唑组中，慢代谢型受试者小肠损伤的发生率显著高于快代谢型受试者（85.7%对31.6%，P = 0.026）。与快代谢型受试者相比，雷贝拉唑组中慢代谢型受试者的黏膜损伤数量也显著更高（中位数[范围]3[0 - 31]对0[0 - 7]，P = 0.01）。此外，我们发现CYP2C19基因型与有塞来昔布诱导小肠损伤风险的受试者同时使用雷贝拉唑之间存在显著相互作用。
当塞来昔布与雷贝拉唑联合使用时，CYP2C19基因型可能与小肠损伤风险相关。
