Shirai N, Furuta T, Xiao F, Kajimura M, Hanai H, Ohashi K, Ishizaki T
First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Aliment Pharmacol Ther. 2002 Apr;16(4):837-46. doi: 10.1046/j.1365-2036.2002.01229.x.
The acid inhibitory effect of lansoprazole depends on the S-mephenytoin 4'-hydroxylase (CYP2C19) genotype status. The effect of famotidine is independent of this genotype.
To investigate the acid inhibitory effects of lansoprazole vs. famotidine during the daytime and night-time with reference to different CYP2C19 genotypes.
Fifteen healthy volunteers were given 20 mg famotidine twice a day or 30 mg lansoprazole once a day for 8 days. On post-dose day 8, 24-h intragastric pH monitoring was performed.
During the daytime, the intragastric pH with lansoprazole was significantly higher than that with famotidine in the heterozygous extensive metabolizer group, whereas no significant difference was observed in the homozygous extensive metabolizer group. During the night-time, the intragastric pH with famotidine was quite similar to that with lansoprazole in the heterozygous extensive metabolizer and poor metabolizer groups. However, during the night-time, the intragastric pH with famotidine was significantly higher than that with lansoprazole in the homozygous extensive metabolizer group.
An insufficient acid inhibition by lansoprazole during the night-time in the homozygous extensive metabolizer group could be compensated for by famotidine. CYP2C19 genotype testing appears to be useful for predicting the optimal acid inhibitory drug treatment collated with circadian intragastric pH change.
兰索拉唑的抑酸作用取决于S-美芬妥英4'-羟化酶（CYP2C19）基因型状态。法莫替丁的作用与该基因型无关。
参照不同的CYP2C19基因型，研究兰索拉唑与法莫替丁在白天和夜间的抑酸效果。
15名健康志愿者每天服用2次20mg法莫替丁或每天服用1次30mg兰索拉唑，共8天。在给药第8天，进行24小时胃内pH监测。
白天，杂合子广泛代谢者组中，服用兰索拉唑后的胃内pH显著高于服用法莫替丁后的；而在纯合子广泛代谢者组中未观察到显著差异。夜间，在杂合子广泛代谢者和慢代谢者组中，服用法莫替丁后的胃内pH与服用兰索拉唑后的相当。然而，在夜间，纯合子广泛代谢者组中，服用法莫替丁后的胃内pH显著高于服用兰索拉唑后的。
在纯合子广泛代谢者组中，夜间兰索拉唑抑酸不足可由法莫替丁弥补。CYP2C19基因型检测似乎有助于预测与昼夜胃内pH变化相匹配的最佳抑酸药物治疗方案。
