Effect of omeprazole 10 mg on intragastric pH in three different CYP2C19 genotypes, compared with omeprazole 20 mg and lafutidine 20 mg, a new H₂‐receptor antagonist

Abstract

SUMMARYBackground: Omeprazole 10 mg is used as maintenance therapy for gastro-oesophageal reflux disease, but previous reports have not mentioned the potency of its acid suppression. Aim: To evaluate the potency of acid suppression with omeprazole 10 mg, in relation to CYP2C19 genotypes. Methods: Eighteen healthy subjects without Helicobacter pylori participated. After a 7-day regimen of omeprazole 10 mg, 20 mg, lafutidine 20 mg (a novel H 2 -receptor antagonist) or water only (baseline data), intragastric pH was measured for 24 h. Results: With omeprazole 10 mg, greater differences were observed than 20 mg in median pH values and pH > 4 holding time ratios between poor metabolizers (PMs, n ¼ 6) and the others [homozygous extensive metabolizers (homo-EMs, n ¼ 6) and heterozygous extensive metabolizers (hetero-EMs, n ¼ 6)]. With lafutidine 20 mg, these parameters were not influenced by the genotype. The potency of acid suppression was: omeprazole 20 mg lafutidine 20 mg > omeprazole 10 mg in homo-EMs, omeprazole 20 mg > omeprazole 10 mg lafutidine 20 mg in hetero-EMs, and omeprazole 20 mg omeprazole 10 mg > lafutidine 20 mg in PMs. Conclusions: Omeprazole 10 mg strongly suppresses acid secretion, but depending on the CYP2C19 genotypes shows greater interindividual variations in suppression than 20 mg.

Acid Suppression Therapy: Where Do We Go from Here?

“…This compound showed a potent and long-lasting inhibition of tiotidine binding and histamine-induced cyclic-3 ,5 -adenosine monophosphate production in Chinese hamster ovary cells expressing human H 2 -receptors [221] . Animal experiments [222] have pointed out that lafutidine has a potent and long-lasting antisecretory effect, a fi nding confi rmed by human investigations [223] showing that this drug inhibits acid secretion more strongly than conventional H 2 -RAs. Conversely from ranitidine and famotidine, lafutidine increases both dayand nighttime intragastric pH in H. pylori -negative subjects [224] , and conversely from omeprazole (and other PPIs) its effi cacy is not infl uenced by the CYP2C19 genotype status [223] .…”

“…Animal experiments [222] have pointed out that lafutidine has a potent and long-lasting antisecretory effect, a fi nding confi rmed by human investigations [223] showing that this drug inhibits acid secretion more strongly than conventional H 2 -RAs. Conversely from ranitidine and famotidine, lafutidine increases both dayand nighttime intragastric pH in H. pylori -negative subjects [224] , and conversely from omeprazole (and other PPIs) its effi cacy is not infl uenced by the CYP2C19 genotype status [223] . When used in combination with antibiotics (namely clarithromycin and amoxicillin) it achieves an eradication rate which is comparable to that of the same PPI-based triple therapy [225] .…”

An open-label, randomized, cross-over bioequivalence study of lafutidine 10 mg under fasting condition

“…Many published comparative clinical studies have established the superiority of lafutidine over proton pump inhibitors [2,6,16] and other H2-receptor antagonists [1,25] . The normal dose of lafutidine is 10 mg once a day for gastric mucosal lesions associated with acute gastritis and acute exacerbation of chronic gastritis; 10 mg once a day as a preanesthetic medication; and 10 mg twice a day for gastric ulcers, duodenal ulcers and stomal ulcers [20] .…”

“…postprandial) as well as during the night [6] . Lafutidine possesses a potent and long lasting gastric antisecretory effect mediated by H2-receptor blockade in animals.…”

Pharmacokinetic and Pharmacodynamic Properties of Lafutidine after Postprandial Oral Administration in Healthy Subjects: Comparison with Famotidine

“…3,4) However, its pharmacodynamics, the relationship between the plasma concentration and the drug response, such as intragastric pH, have not been reported. We believe it is clinically important to examine differences between lafutidine and famotidine to clarify the positioning of lafutidine in H 2 -receptor antagonists, because famotidine is the most commonly used H 2 -receptor antagonist in Japan.…”