ABSTRACT
The polymorphism of CYP2C19 gene constitutes the basis for the difference in enzyme activity and affects the metabolism of many drugs including proton pump inhibitors.The distribution of CYP2C19 gene varies by region and race.The study on the relationship between CYP2C19 genotype and proton pump inhibitors is of great significance for the individualized treatment of Helicobacter pylori (Hp) in children.This paper reviews the effects of CYP2C19 gene polymorphism on proton pump inhibitors and the efficacy of Hp eradication in children.
ABSTRACT
Objective:To investigate the distribution of CYP2C19 genotypes in Helicobacter pylori (Hp) infected children in Chongqing and the correlation of genotypes with gender, age and efficacy, and to provide a reasonable plan for Hp eradication in children in Chongqing. Methods:A prospective clinical cohort study was carried out on 156 children who were suspected of Hp infection and underwent gastroscopy in Children′s Hospital of Chongqing Medical University from March to July 2020. 13C-urea breath test ( 13C-UBT), rapid urease test (RUT) and histological examination were made for all the children included.Meanwhile, for Hp-positive children, the CYP2C19 genotypes were detected by using the polymerase chain reaction(PCR)-sequence-specific primer method, and their sensitivity to Clarithromycin and Amoxicillin was assessed.According to the genetic testing results, the CYP2C19 genotypes were divided into homozygous extensive metabolizer (HomEM), heterozygous extensive metabolizer (HetEM) and poor metabolizer (PM). The eradication outcomes of proton pump inhibitor combined with Amoxicillin and Clarithromycin (PAC) in different genotypes were observed.The measurement data that did not conform to the normal distribution were expressed with the median ( M), and the enumeration data were represented by the rate or the constituent ratio.The Chi- square test was used for comparison between groups, and P<0.05 indicated statistically significant difference. Results:(1)A total of 102 children were Hp positive.Positive rates of 13C-UBT, RUT and histologic results were 97.1% (99/102), 99.0% (101/102), and 90.2% (92/102), respectively.(2)Among the 102 Hp-infected children HomEM accounted for 45.1% (46/102), HetEM for 41.2% (42/102), and PM for 13.7% (14/102). (3)There were 50 males and 52 females in 102 Hp-infected children.The age range was 3 years to 17 years and 9 months (median: 9 years and 7 months). There was no significant difference in the distribution of CYP2C19 genotypes between females and males and among children of different ages (all P>0.05). (4)In 87 cases treated with PAC regimen, 36 cases failed to eradicated Hp in the initial treatment, including 18 cases of HomEM, 15 cases of HetEM, and 3 cases of PM.Hp was eradicated successfully in 51 cases, including 21 cases of HomEM, 21 cases of HetEM and 9 cases of PM.There was no statistically significant difference in the Hp eradication efficacy among children with different CYP2C19 genotypes treated by the PAC regimen ( P>0.05). (5) Among the 87 children, 45 children were sensitive to Clarithromycin, and 37 of them achieved successful Hp eradication.About 42 children were resistant to Clarithromycin, and Hp eradication was fulfilled in 14 of them.There was a statistically significant difference in the Hp eradication efficacy among Clarithromycin-resistant children treated by PAC regimen ( P<0.05). Conclusions:The CYP2C19 genotypes have no correlation with gender, age and Hp eradication efficacy of PAC in children with Hp infection in Chongqing.
ABSTRACT
Objective: To investigate acid-suppression efficacy of proton pump inhibitors (PPIs) in relation to CYP2C19 genetic polymorphism on patients with peptic ulcer. Methods: By an open, randomized and control trial, fifty nine patients with active peptic ulcer were randomly assigned to receive one of three PPIs on a single dose (20 mg of each drug): omeprazole group (n = 19), rabeprazole group (n = 20) and esomeprazole group (n = 20). Intragastric pH was recorded 1 hour before and 24 hours after administration. CYP2C19 genotype was tested in all patients. Results: The EMs/PMs ratio of each group was 16/3,17/3 and 17/3, respectively. The total time that intragastric pH>4, time percent pH>4 and median pH in PMs patients were significantly higher than those in EMs patients of omeprazole group (P < 0.05). But all these differences were not found in rabeprazole group and esomeprazole group. The pH of nocturnal acid breakthrough (NAB) in both rabeprazole group and esomeprazole group was higher than that of omeprazole group, while there was no significant difference between rabeprazole group and esomeprazole group. Conclusion: The acid-suppression efficacy of omeprazole is highly dependent on CYP2C19 genetic polymorphism, while CYP2C19 genetic polymorphism may have a little influence on the acid-suppression efficacy of rabeprazole and esomeprazole. The acid-suppression action of rabeprazole and esomeprazole is superior to omeprazole, especially on night acid secretion.
ABSTRACT
Obiective To investigate acid-suppression efficacy of proton pump inhibitors(PPls) in relation to CYP2C19 genetic polymorphism on patients with peptic ulcer. Methods By an open, randomized and control trial, fifty nine patients with active peptic ulcer were randomly assigned to receive one of three PPIs on a single dose (20 mg of each drug): omeprazole group (n=19), rabeprazole group (n=20) and esomeprazole group (n=20). lntragastric pH was recorded 1 hour before and 24 hours after administration. CYP2C19 genotype was tested in all patients. Resuits The EMs/PMs ratio of each group was 16/3,17/3 and 17/3, respectively. The total time that intragastric pH＞4, time percent pH＞4 and median pH in PMs patients were significantly higher than those in EMs patients of omeprazole group (P＜0.05). But all these differences were not found in rabeprazole group and esomeprazole group. The pH of nocturnal acid breakthrough (NAB) in both rabeprazole group and esomeprazole group was higher than that of omeprazole group, while there was no significant difference between rabeprazole group and esomeprazole group. Gonclusion The acid-suppression efficacy of omeprazole is highly dependent on CYP2C19 genetic polymorphism, while CYP2C19 genetic polymorphism may have a little influence on the acid-suppression efficacy of rabeprazole and esomeprazole. The acid-suppression action of rabeprazole and esomeprazole is superior to omeprazole, especially on night acid secretion.