Effect of concomitant dosing of famotidine with lansoprazole on gastric acid secretion in relation to CYP2C19 genotype status

Abstract

Background: Famotidine increases Helicobacter pylorieradication rates by a triple lansoprazole/amoxicillin/ clarithromycin therapy in patients with the rapid extensive metabolizer genotype of CYP2C19. Aim: To determine the effect of famotidine on the gastric acid inhibition by lansoprazole in relation to CYP2C19 genotypes. Methods: Twenty healthy volunteers with different CYP2C19 genotypes -consisting of six rapid extensive metabolizers, nine intermediate metabolizers and five poor metabolizers -underwent three 7-day courses with placebo, lansoprazole 30 mg twice daily, and lansoprazole 30 mg twice plus famotidine 20 mg twice daily. Lansoprazole was dosed after breakfast and dinner. Famotidine was dosed after lunch and at bedtime.

Early effects of Lansoprazole orally disintegrating tablets on intragastric pH in CYP2C19 extensive metabolizers

“…Each report differs slightly, but CYP2C19 genotype status is shown to influence gastric acid suppression by LPZ and most other PPIs. The metabolism of LPZ, OPZ and other PPIs is affected by the CYP2C19 polymorphism, and the plasma PPI level and intragastric pH values of EMs are significantly lower than those of PMs [20][21][22] . On the other hand, several studies have demonstrated that after a dose of RPZ, intragastric pH is not affected by the CYP2C19 polymorphism on 3 d-7 d of treatment [17][18][19]38,39] .…”

“…The genetic mutation was analyzed by either the polymerase chain reactionrestriction fragment length polymorphism (PCR-RFLP) method [24] or the TaqMan polymerase chain reaction amplification method (Applied Biosystems Japan, Chiba, Japan) [25] . Based on point mutations in exons 4 and 5 of the CYP2C19 gene, individuals can be classified into homo-extensive metabolizers (homo-EMs), hetero-extensive metabolizers (hetero-EMs) and poor metabolizers (PMs) [20][21][22] . Homo-EMs have the wild type alleles (wt/wt) without any mutations in exons 5 and 4; PMs have mutated alleles (m1/m2) with mutations in both exons 5 and 4 (m1/m2, m1/m1 or m2, m2); and hetero-EMs have a mutated allele in either exon 5 or 4 (wt/m1 or wt/m2).…”

“…According to these reports, the metabolism of PPIs is affected by the CYP2C19 polymorphism; the plasma PPI levels and intragastric pH values in extensive metabolizers are significantly lower than those in poor metabolizers [20][21][22] . Therefore, in this study, the subjects were all CYP2C19 extensive metabolizers.…”

Refractory Ulcer of Reconstructed Gastric Tube after Esophagectomy: A Case Report

“…[11][12][13][14] Based on point mutations in exons 4 and 5 of the CYP2C19 gene, individuals can be classified as homo-EMs, hetero-EMs and poor metabolizers (PMs) . 15,16) In Japan, the frequency of the homo-EM phenotype is the highest (34.9%), followed by hetero-EM (46.3%), and PM phenotype (18.8%).…”

In vitro effects of famotidine and ranitidine on lower esophageal sphincter tone in rats

“…H 2 blockers such as famotidine, nizatidine and roxatidine are excreted in the urine with little involvement in hepatic metabolism and are not affected by the polymorphisms present in hepatic enzymes. Drug interactions are also not common among them (40). Furthermore, H 2 blockers inhibit nocturnal acid secretion that depends largely on histamine as well (41).…”