Role of Omeprazole Dosage and Cytochrome P450 2C19 Genotype in Patients Receiving Omeprazole‐Amoxicillin Dual Therapy for Helicobacter pylori Eradication

Abstract

Provided a maintenance dose of amoxicillin is given every 6 hours, eradication of H. pylori infection was significantly dependent on omeprazole dosage, CYP2C19 genotype, age, gastritis status, and H. pylori density.

Role of bismuth in improvingHelicobacter pylorieradication with triple therapy

“…However, work has continued on identifying factors influencing the effectiveness of PPI therapy in healing ulcers and erosive oesophagitis, especially the relationship with role of CYP2C19 polymorphisms and the metabolism of PPIs. Slow PPI metabolism results in prolonged duration of PPI effect resulting in enhanced ulcer cure rates and prolonged increases in gastric pH, which increases the effectiveness of dual therapy 80 81 97–103. Current data suggest the effectiveness of dual therapy most depends on the ability to consistently obtain and maintain an intragastric pH of 6 or greater 80 100 102 104–106…”

“…The 40 and 60 mg doses were equivalent and only maintained a pH of 6 or greater for 13 h and at pH 7 for 5 h 102. Yang et al 81 evaluated the roles of once or two times per day omeprazole dosing and 250 and 500 mg of amoxicillin four times daily, CYP2C19 genotype, intragastric pH, and presence of gastric corpus inflammation on outcome of 14-day dual omeprazole–amoxicillin therapy. Based on the concept that the bactericidal activity of β-lactam antibiotics is time rather than concentration dependent,109 they used every 6 h amoxicillin dosing to attempt to maintain the MIC within the effective range 81.…”

“…Yang et al 81 evaluated the roles of once or two times per day omeprazole dosing and 250 and 500 mg of amoxicillin four times daily, CYP2C19 genotype, intragastric pH, and presence of gastric corpus inflammation on outcome of 14-day dual omeprazole–amoxicillin therapy. Based on the concept that the bactericidal activity of β-lactam antibiotics is time rather than concentration dependent,109 they used every 6 h amoxicillin dosing to attempt to maintain the MIC within the effective range 81. Furuta et al have long emphasised that in order to reliable achieve cure rates over 90%, it is important to administer amoxicillin approximately every 6 h and maintain the pH at 6 or above 80 110.…”

Rapid metabolizer genotype of CYP2C19 is a risk factor of being refractory to proton pump inhibitor therapy for reflux esophagitis

“…45 Further, treatment for eradication of H. pylori fails when acid secretion is not sufficiently inhibited. [46][47][48] As a first-line treatment, PPIs effectively improve acid-reflux symptoms and esophageal mucosal breaks. [9][10][11]49 However, given that CYP2C19 polymorphisms influence both pharmacokinetics (e.g.…”

Potent Gastric Acid Inhibition Over 24 Hours by 4-Times Daily Dosing of Esomeprazole 20 mg

“…Intragastric pH during treatment is associated with the cure rate of treating peptic ulcers [23], GERD [24] and aspirin-induced gastrointestinal mucosal injury [25]. Further, the eradication treatment for H. pylori infection fails if the inhibition of acid secretion during therapy is insufficient [26,27,28]. Twenty-four-hour pH monitoring studies during PPI treatment in refractory GERD patients (20% patients with erosive esophagitis and 40-50% NERD patients) revealed pH values <4.0 at certain time points [29,30,31], resulting in prolonged and frequent exposure of the esophageal mucosa to refluxed acidic gastric juice [32].…”