Diffferent Dose Esomeprazole-based Triple Therapy For Helicobacter Pylori Infection And The Effect On The Distribution Of Amoxicillin In The Human Stomach

Objective:To prospectively compare efficacies of standand-dose verus high-dose esomeprazole-based tirple therapy and levofloxacin-based tirple therapy for Helicobacter pylori(Hp) infection. To compare the effecies of high-dose verus standand-dose esomeprazole-based tirple therapy on the distribution of amoxicillin in the human stomach and plasma.Methods:Three hundred and sixty patients with chronic gastritis or peptic ulcer who were positive for Hp infection confirmed by gastroscopy and 14C urea breath test(14C-UBT) were randomly divided into three groups: high-dose group(E40AC group n=120): esomeprazole(40 mg b.d.) combined with clarithromycin (500 mg b.d.) and amoxicillin (1 g b.d.) for 10 days; standard-dose group (E20AC group n=120): esomeprazole(20 mg b.d.) combined with clarithromycin (500 mg b.d.) and amoxicillin (1 g b.d.) for 10 days; levofloxacin-based group(ELA group n=120): levofloxacin (500 mg,qd)combined with amoxicillin (1 g b.d.) and esomeprazole 20 mg b.d for 7 days。Follow-up 14C urea breath test (14C-UBT) was performed at four to eight weeks after the end of the treatment.The patients who were informed consent to attend the study determined the concentrations of amoxicillin in stomach and plasma. The blood sample, gastric juice and gastric mucosa tissue samples were collected during endoscopy at 2 hours after the morning administration on day 10. Concentrations of amoxicillin in human plasma, gastric juice and gastric mucosa samples were determined by high performance liquid chromatography (HPLC) in Waters 515 HPLC system.Results:(1)324 patients completed the study. Hp eradication rate was 78.3% with E40AC group and 75.8% with E20AC group and 76.7% with ELA group by intention-to-treat(ITT) analyses with no significant difference(P = 0.896).whereas Hp eradication was 86.2% with E40AC group and 82% with E20AC group and 88.5% with ELA group by per-protocol(pp) analyses without difference(P = 0.388). Hp eradication rate of peptic ulcer diseases patients was higher than chronic gastritis patients with significant difference(P =0.004,0.035) both by intention-to-treat analyses and per-protocol analyses.(2)Univariate analysis showed that Hp eradication rate of peptic ulcer diseases patients was higher than chronic gastritis patients with significant difference(P = 0.005). The other factors (sex, age, alcohol consumption, smoking, tea consumption) were not markedly associated with Hp eradication rates. Multivariate analysis disclosed that peptic ulcer diseases was the only independent factor for Hp eradication. The odds ratios(OR)were 0.326 (95% confidence interval (CI), 0.150-0.710,P = 0.005).(3) Amoxicillin concentration in the gastric juice was obviously higher than that in the plasma and gastric mucosa at 2 hours after administration in both high-dose group and standard-dose group(P= 0.009,0.01,0.025,0.018),Amoxicillin concentration in the gastric juice was 4.3 times of that in the plasma, and 4-5 times of that in the gastric mucosa. Amoxicillin concentration have no differences between gastric corpus and gastric antrum(P=0.917,0.912). Amoxicillin concentration have no differences between gastric mucosa and plasma in both high-dose group and standard-dose group(P = 0.501,0.306,0.16,0.058). Amoxicillin concentration in plasma, gastric mucosa, and gastric juice samples in high-dose group was higher than that in standard-dose group with no significant difference(P = 0.437,0.588,0.351,0.082).The ratios of amoxicillin concentration of gastric mucosa and gastric juice and plasma in high-dose group were also higher than that in standard-dose group with no significant difference(P =0.578,0.572,0.498).Conclusion:1) A similar higher Hp eradication was achieved by either high-dose or standard-dose esomeprazole-based triple regimen.2) The 7-d triple therapy with esomeprazole, amoxicillin and levofloxacin will be effective to eradicate Hp, and cause fewer adverse reactions. The regimen can be used as replacement therapy of standand tirple therapy.3) Hp eradication rate of peptic ulcer diseases patients was higher than chronic gastritis patients with significant difference. Peptic ulcer diseases was the only independent factor for Hp eradication rate.4) Amoxicillin concentration of plasma, gastric mucosa, and gastric juice samples in high-dose group were the same as in standard-dose triple. To increase esomeprazole dose had no effect on amoxicillin concentration of plasma, gastric mucosa, and gastric juice samples in Hp -infected patients.