Relationship between the Acid-Inhibitory Effects of Two Proton Pump Inhibitors and CYP2C19 Genotype in Japanese Subjects: A Randomized Two-Way Crossover Study
Relationship between the Acid-Inhibitory Effects of Two Proton Pump Inhibitors and CYP2C19 Genotype in Japanese Subjects: A Randomized Two-Way Crossover Study
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日本受试者中两种质子泵抑制剂的酸抑制作用与 CYP2C19 基因型之间的关系：随机双向交叉研究
DOI：
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发表时间：
2010
影响因子：
1.6
通讯作者：
Y. Kinoshita
中科院分区：
文献类型：
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作者：
K. Furuta;K. Adachi;S. Ohara;T. Morita;T. Tanimura;K. Koshino;Y. Kinoshita
这项双向交叉研究研究了质子泵抑制剂奥美拉唑和雷贝拉唑对不同细胞色素P450家族2亚家族C多肽19（CYP 2C 19）基因型的日本受试者胃酸分泌影响的可能差异。共有23名幽门螺杆菌阴性的健康志愿者接受奥美拉唑20 mg/d和雷贝拉唑10 mg/d治疗。每种药物治疗以随机顺序分配，连续7天，药物治疗期之间至少间隔1周，以允许洗脱。在第1天和第7天测量胃内pH值。奥美拉唑组首次给药后7和8 h的总体胃内pH中位值水平显著较高。在首次给药后6、7和8 h，纯合子快代谢者的胃内pH值无显著差异，而在杂合子快代谢者和慢代谢者的合并数据中，奥美拉唑组胃内pH值显著较高。在给药第7天，奥美拉唑和雷贝拉唑之间的胃内pH值无显著差异，与基因型无关。总之，在CYP 2C 19弱代谢型基因型发生率较高的日本个体中，第1天20 mg/天奥美拉唑的抗分泌作用起效时间比10 mg/天雷贝拉唑更快，但到第7天，无论基因型如何，均未发现抗分泌作用存在差异。
This two-way crossover study investigated possible differences between the proton pump inhibitors, omeprazole and rabeprazole, in their effect on gastric acid secretion in Japanese subjects with differing cytochrome P450, family 2, subfamily C, polypeptide 19 (CYP2C19) genotypes. A total of 23 Helicobacter pylori-negative healthy volunteers received omeprazole 20 mg/day and rabeprazole 10 mg/day. Each drug treatment was given for a continuous 7-day period allocated in random order, with an interval of at least 1 week between drug treatment periods to allow for wash-out. Intragastric pH was measured on days 1 and 7. Overall median intragastric pH levels at 7 and 8 h after the first administration were significantly higher with omeprazole. There was no significant difference in intragastric pH in homozygous extensive metabolizers, whereas intragastric pH was significantly higher with omeprazole in combined data from heterozygous extensive metabolizers and poor metabolizers at 6, 7 and 8 h after the first drug administration. There were no significant differences in intragastric pH between omeprazole and rabeprazole irrespective of genotype on day 7 of administration. In conclusion, on day 1 the time to onset of the antisecretory action of 20 mg/day omeprazole was more rapid than that of 10 mg/day rabeprazole in Japanese individuals who have a higher incidence of the CYP2C19 poor metabolizer genotype, however by day 7 no difference in antisecretory effect was found, regardless of genotype.
兰索拉唑代谢中涉及的人类 P450 酶的鉴定。
DOI：
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发表时间：
1996
期刊：
The Journal of pharmacology and experimental therapeutics.
影响因子：
--
作者：
Pearce,RE;Rodrigues,AD;Goldstein,JA;Parkinson,A
通讯作者：
Parkinson,A
影响因子：
3.6
作者：
S. M. Morais;G. Wilkinson;J. Blaisdell;U. Meyer;K. Nakamura;J. Goldstein
通讯作者：
S. M. Morais;G. Wilkinson;J. Blaisdell;U. Meyer;K. Nakamura;J. Goldstein