Aciphex
Direct effects of proton pump inhibitors on histamine release from rat enterochromaffin-like cells.

Yokota T, Matsui H, Matsuura B, Maeyama K, Onji M.

Third Department of Internal Medicine, Ehime University School of Medicine, Shigenobu-cho, Onsen-gun, Ehime-ken, Japan.

Enterochromaffin-like (ECL) cells play a central role in the regulation of gastric acid secretion. Previous studies have shown that proton pump inhibitors accelerate histamine release from ECL cells through the effects of gastrin. However, direct effects of proton pump inhibitors on ECL cells have not been demonstrated to date because the indirect effects of gastrin are difficult to suppress. We investigated the direct effects of proton pump inhibitors medication on ECL cells using an elutriation system. ECL cells were stimulated with gastrin or rabeprazole, and histamine release from ECL cells was measured. Rabeprazole increased histamine release through a pathway that differed from that of gastrin. The histamine increase was likely due to an acceleration of vesicular monoamine transporter 2 (VMAT2). Rabeprazole increased histamine release from ECL cells directly via VMAT2, but did not affect the total amount of histamine in the cells. The results suggest that patients receiving proton pump inhibitors for extended periods must be monitored extensively because gastric tumor proliferation may be promoted by increased histamine release from ECL cells.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14642791&dopt=Abstract rabeprazole Aciphex



Aciphex
Rabeprazole 10 mg twice daily is superior to 20 mg once daily for night-time gastric acid suppression.

Shimatani T, Inoue M, Kuroiwa T, Horikawa Y.

Department of General Medicine, Hiroshima University Hospital, Hiroshima, Japan. tshima hiroshima-u.ac.jp

BACKGROUND: Insufficient acid suppression is one of the main causes of proton pump inhibitor-refractory gastro-oesophageal reflux disease. AIM: To achieve more potent and long-lasting acid suppression, different dosage regimens of rabeprazole were compared in relation to the CYP2C19 genotype status. METHODS: In a cross-over study, 18 healthy Helicobacter pylori-negative males (six homozygous extensive metabolizers, six heterozygous extensive metabolizers and six poor metabolizers) were given rabeprazole 10 mg once daily, 20 mg once daily or 10 mg twice daily, or water only (baseline data), for 7 days each. On day 7 of each regimen, 24-h intragastric pH-metry was performed. RESULTS: No significant differences were observed in median pH values and pH>4 holding time ratios between rabeprazole 10 mg once daily and 20 mg once daily. However, with rabeprazole 10 mg twice daily, these parameters were significantly higher than those with 20 mg once daily. The potency of acid suppression by rabeprazole was influenced by the CYP2C19 genotype status. The differences were somewhat significant but not large. The incidence of nocturnal acid breakthrough was lowest with rabeprazole 10 mg twice daily. CONCLUSIONS: Rabeprazole 10 mg twice daily, not 20 mg once daily, should be administered to achieve more potent and long-lasting acid suppression.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14687173&dopt=Abstract rabeprazole Aciphex



Aciphex
Efficacy of triple therapy with rabeprazole for Helicobacter pylori infection in relation to CYP2C19 genotype.

Lee SB, Park SJ, Ryu JK, Lee JK, Kim HJ, Bae JS, Jung HS, Park SM.

Department of Internal Medicine, Bundang Jesaeng General Hospital, Seongnam-si, Gyeonggi-do, Korea.

BACKGROUND/AIMS: Genetic polymorphism of cytochrome P450 CYP2C19 influences the efficacy of proton pump inhibitor (PPI) in Helicobacter pylori (H. pylori) eradication therapy. We investigated the difference in the cure rates of H. pylori infection by triple (rabeprazole plus amoxacillin and clarithromycin) therapy in relation to CYP2C19 genotype status. METHODS: One hundred and sixteen H. pylori infected patients with gastric ulcer and duodenal ulcer completed the triple therapy with 10 mg of rabeprazole b.i.d., 1,000 mg amoxacillin b.i.d. and 500 mg of clarithromycin b.i.d. for one week. The genotype of CYP2C19 was determined by a PCR-restriction fragment length polymorphism method. RESULTS: According to the univariate analysis, heterozygous extensive metabolizers (hetero EMs) and poor metabolizers (PMs) showed the highest (87.0%) and the lowest (80.0%) eradication rates, respectively. The difference in the therapeutic efficacy of rabeprazole among the different CYP2C19 genotypes was insignificant. With regard to gender, age and smoking history in relation to eradication rate, a statistical significance was noted only with age with odds ratio of 1.063 and p-value of 0.0202. CONCLUSIONS: In the eradication therapy of H. pylori, no statistically significant difference in therapeutic efficacy of rabeprazole was found among different CYP2C19 genotypes.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14695703&dopt=Abstract rabeprazole Aciphex