Administration Of Rabeprazole Research Articles

Small Bowel Electrical Activity in an Experimental Model of Hypochlorhydria

Variations in the basic parameters of the electrical activity of the small intestine in rats were studied using an experimental model of hypochlorhydria caused by an intragastric administration of rabeprazole for 16 days. Hypochlorhydria was found to lead to an increased duration of irregular electric activity and a reduction in the period of quiescence, which indicates an increase in uncoordinated contractions of the small intestine. A decrease in the number of migrating myoelectric complexes and, consequently, a partial suppression of propulsive peristalsis contributes to an excessive bacterial overgrowth in the proximal small intestine.

Evaluations of Gastric Acid Pocket Using Novel Vertical 8-Channel pH Monitoring System and Effects of Acid Secretion Inhibitors.

Background/AimsThe gastric acid pocket has an important role in gastroesophageal reflux disease development. In this study, we utilized a novel 8-channel pH monitoring system with sensor intervals of 1 cm on the vertical axis for evaluation of postprandial gastric acid pocket in healthy Japanese adults, as well as the effects of vonoprazan and rabeprazole.MethodsTwelve healthy volunteers without Helicobacter pylori infection were enrolled. A catheter was inserted transnasally and positioned under X-ray guidance, then postprandial acid pocket formation was monitored over time in a sitting position. Thereafter, acid pocket changes were assessed following administration of vonoprazan (20 mg) or rabeprazole (20 mg).ResultsThe gastric acid pocket was successfully measured by use of the present system in 10 cases, while failure occurred in 2 because of inappropriate catheter positioning. Observed acid pockets were visualized with a mean length of 2.2 ± 0.4 channels on the top layer of food contents approximately 20 minutes after finishing a meal. There were some variations for lasting time of the acid pocket. Complete elimination within 3 hours after administration of vonoprazan was noted in all cases. Likewise, following administration of rabeprazole, the acid pocket was eliminated in 7 cases, while acidity was reduced though the pocket remained observable in 3.ConclusionsGastric acid pocket observations were possible using our novel vertical 8-channel sensor catheter. The present findings showed that vonoprazan strongly suppressed acid secretion within a short period, suggesting its effectiveness for gastroesophageal reflux disease treatment.

Gastric acid inhibitor aggravates indomethacin-induced small intestinal injury via reducing Lactobacillus johnsonii

Proton pump inhibitors (PPIs) alter the composition of the intestinal microbiome, exacerbating indomethacin (IND)-induced small intestinal damage. Vonoprazan fumarate inhibits gastric acid secretion using a different mechanism from PPIs. We investigated the effects of both drugs on the intestinal microbiome and IND-induced small intestinal damage. We sought to clarify whether PPI-induced dysbiosis and worsening of the damage were due to a specific drug class effect of PPIs. Rabeprazole administration increased operational taxonomic unit numbers in the small intestines of C57BL/6 J mice, whereas the difference was not significant in the vonoprazan-treated group but exhibited a trend. Permutational multivariate analysis of variance of the unweighted UniFrac distances showed significant differences between vehicle- and vonoprazan- or rabeprazole-treated groups. L. johnsonii was the predominant microbial species, and the population ratio decreased after vonoprazan and rabeprazole administration. The vonoprazan- and rabeprazole-treated groups showed increased IND-induced damage. This high sensitivity to IND-induced damage was evaluated by transplantation with contents from the small intestine of mice treated with either vonoprazan or rabeprazole. Supplementation of L. johnsonii orally in mice treated with rabeprazole and vonoprazan prevented the increase in IND-induced small intestinal damage. In conclusion, both rabeprazole and vonoprazan aggravated NSAID-induced small intestinal injury by reducing the population of L. johnsonii in the small intestine via suppressing gastric acid secretion.

Early effect on intragastric pH of oral administration of rabeprazole with mosapride compared with rabeprazole alone.

BackgroundAn ideal medication for acid-related diseases would offer prompt stopping of blood flow as well as efficient symptom resolution. The aim of this study was to investigate the gastric acid suppression potency of a single oral dose of rabeprazole alone, compared with administration of rabeprazole plus mosapride.MethodsTwelve male volunteers, Helicobacter pylori (H. pylori)-negative, participated in this randomized, three-way crossover study. After a single oral administration of rabeprazole, rabeprazole with mosapride, or rabeprazole administered 1 h after mosapride, we monitored their intragastric pH constantly for 6 h. A 7-day washout period was allowed between each administration.ResultsThe median 6-h intragastric pH after the administration of rabeprazole 1 h after mosapride was 4.41±1.22 (mean±s.d.), significantly higher than after rabeprazole alone 3.45±1.33, P=0.0376). There was no significant difference between the median 6-h pH after the administration of rabeprazole plus mosapride and that after rabeprazole alone (3.81±0.98 vs. 3.45±1.33, respectively; P=0.0927).ConclusionAn oral dose of rabeprazole administered 1 h after mosapride increased the intragastric pH more rapidly than rabeprazole alone, in healthy, male, H. pylori-negative volunteers.

The Effect of Rabeprazole on the Antiplatelet Efficacy of Clopidogrel: A Systematic Review

Introduction: Clopidogrel is a P2Y12 receptor antagonist given to patients with coronary heart disease, usually in combination with aspirin. It is metabolized to its active component through the cytochrome P450 2C19 (CYP2C19) isoenzyme. Proton pump inhibitors (PPI) are commonly used in patients who are receiving clopidogrel, especially those at high-risk for gastrointestinal bleeding. However, certain PPIs are likewise metabolized through the CYP2C19 isoenzyme. Co-administration of the two classes of drugs may lead to lower levels of clopidogrel, leading to lower antiplatelet efficacy and lower effects on cardiovascular disease prevention of the drug. Objective: To determine the effects of rabeprazole on platelet activity, major adverse cardiovascular outcomes and gastrointestinal bleeding among patients receiving clopidogrel Methodology: We performed this meta-analysis that included all types of studies (randomized controlled trials, case control studies, prospective and retrospective cohort studies) that investigated rabeprazole versus no rabeprazole or placebo. The population consisted of patients who received clopidogrel for any indication with concomitant administration of rabeprazole versus clopidogrel alone. Randomized trials were assessed using Cochrane’s Collaboration tool for assessment of risk of bias. For non randomized studies, Newcastle-Ottawa Quality Assessment Scale for cohort studies was used. Dichotomous data were analyzed using risk ratio and 95% confidence interval, while continuous variables were analyzed using mean differences and standard deviation. Heterogeneity was tested using chi-square test and I2 statistics. Results: There were no statistically significant differences noted in the outcomes of maximal platelet aggregation (mean difference 0.75, 95% CI -3.85 to 5.35), platelet reactivity index (mean difference -0.75, 95% CI -5.11 to 3.61), total cardiovascular events (RR 2.64, 95% CI 0.65 to 10.75) and gastrointestinal bleeding (RR 0.72, 95% CI 0.34 to 1.55) between clopidogrel-treated patients on rabeprazole compared to those without.. Data were not heterogenous, except on the outcome of total cardiovascular events. An influence analysis showed that removal of one trial made the outcome non-heterogenous, but the outcome difference was still not statistically significant (RR 1.25, 95% CI 0.66 to 2.37). Conclusion: Rabeprazole in addition to clopidogrel did not significantly affect maximal platelet aggregation, platelet reactivity index, gastrointestinal bleeding and cardiovascular outcomes.

Population Pharmacokinetics of Rabeprazole and Dosing Recommendations for the Treatment of Gastroesophageal Reflux Disease in Children Aged 1–11 Years

Rabeprazole sodium is a proton pump inhibitor used for the treatment of gastroesophageal reflux disease (GERD). The objective of this study was to develop a population pharmacokinetic model for rabeprazole that describes concentration-time data arising from phaseI and phaseIII studies in adult and pediatric subjects, including neonates and preterm infants, and propose dosing recommendations for pediatric subjects aged 1-11years. A total of 4,417 pharmacokinetic observations from 597 subjects aged 6days to 55.7years with body weights of 1.15-100kg were used to develop the population pharmacokinetic model using non-linear mixed-effects modeling techniques. Weight and age were included in the structural model to describe clearance (CL) and central volume of distribution (V c). Other covariates considered during model development included sex, race, creatinine clearance, hepatic function, formulation, feeding status, and route of administration. The final model was used to determine doses for pediatric subjects aged 1-11years to achieve a steady-state area under the plasma concentration-time curve across the dose interval of 24h (AUC24) within the target adult AUC24 range obtained following a rabeprazole 10mg dose. The best model was a two-compartment disposition model with a sequential zero-order duration of input (Dur), first-order absorption (k a) following a lag time (T lag), with weight and age effects on CL and V c. Formulation type and feeding status described some of the variability in bioavailability and the absorption parameters T lag, Dur, and k a. A dosage regimen of 5mg once daily for children <15kg, and 10mg for children ≥15kg is recommended for 1- to 11-year-old pediatric patients with GERD. The pharmacokinetics of rabeprazole were described with good precision following administration of rabeprazole across a range of doses and in a range of formulations.

Rabeprazole exhibits antiproliferative effects on human gastric cancer cell lines.

Intracellular proton extrusion in gastric cancer cells has been reported to promote cancer cell survival under acidic conditions via hydrogen/potassium adenosine triphosphatase (H+/K+-ATPase). Rabeprazole is a frequently used second-generation proton pump inhibitor (PPI) that irreversibly inactivates gastric H+/K+-ATPase. Therefore, we hypothesized that rabeprazole could reduce the viability of gastric cancer cells. In the present study, four human gastric cancer cell lines and one non-cancer gastric cell line were cultured. Cell viability, the α- and β-subunits of H+/K+-ATPase and cellular apoptosis were analyzed by dye exclusion assay, reverse transcription-polymerase chain reaction and annexin V-fluorescein isothiocyanate/propidium iodide staining, respectively. The expression level of total extracellular signal-regulated protein kinase 1/2 (ERK 1/2) and phosphorylated-ERK protein was detected by western blot analysis. Gastric cancer cell lines were more tolerant of the acidic culture media than non-cancer cells. Administration of rabeprazole led to a marked decrease in the viability of MKN-28 cells. Exposure to rabeprazole induced significant apoptosis in AGS cells. Rabeprazole completely inhibited the phosphorylation of ERK 1/2 in the MKN-28 cells, whereas the same effect was not observed in either the KATO III or MKN-45 cells. The ERK 1/2 inhibitor, PD98059, attenuated the viability of the AGS cells. A similar antiproliferative effect was observed in the rabeprazole treatment group. In addition, PD98059 and rabeprazole were able to efficaciously inhibit the phosphorylation of ERK 1/2 in the gastric cancer cells. Therefore, it was concluded that rabeprazole can attenuate the cell viability of human gastric cancer cells through inactivation of the ERK1/2 signaling pathway. The results of the present study demonstrate that rabeprazole inhibits the viability of gastric cancer cells in vitro and may serve as a novel antineoplastic agent.

Preprocedural Rabeprazole Treatment Before Endoscopic Submucosal Dissection for Gastric Neoplasms

The maximal effect of proton pump inhibitors (PPI) is reported to take 5 days. However, most current protocols start PPI on the day of gastric endoscopic submucosal dissection (ESD). We aimed to evaluate the benefit of 5 days pretreatment with oral PPI before ESD to prevent bleeding. This was a prospective randomized controlled trial. Patients were administered oral rabeprazole 20 mg or placebo twice daily for 5 days before ESD. Intravenous pantoprazole 40 mg was administered 2 h before ESD and at postprocedure day 1, and then oral rabeprazole 20 mg was administered once daily. Follow-up endoscopy was performed on days 1 and 30. Forty-eight-hour measurement of intragastric pH was performed in 26 patients. The primary endpoint was major bleeding related to ESD. One-hundred and twenty patients were enrolled. Of these, 45 in the pretreatment and 53 in the placebo group were analyzed. Each group had three cases of major bleeding. There were no significant differences in the ulcer healing rate. Intragastric pH percentage times greater than 4, 5, and 6 were 86.61 ± 19.45 %, 83.30 ± 22.06 %, and 76.86 ± 25.35 %, respectively, in the pretreatment and 85.54 ± 19.45 %, 84.08 ± 27.11 %, and 81.53 ± 27.81 %, respectively, in the placebo group, without significant differences. Preprocedural administration of rabeprazole offers no additional benefit over postprocedural administration alone in preventing major bleeding after gastric ESD.

Intra-gastric pH following single oral administrations of rabeprazole and esomeprazole: double-blind cross-over comparison.

Comparisons between the acid inhibitory effects of rabeprazole and esomeprazole after single oral administration with standard doses have not been previously presented. We examined intra-gastric pH after oral administrations of these two proton pump inhibitors using 24-h pH monitoring. Fifty-four normal volunteers not infected by Helicobacter pylori were investigated. Using a cross-over design, we administered 10 mg of rabeprazole or 20 mg of esomeprazole in 27 at 30 min after supper and in the remaining 27 subjects at 15 min before supper, and performed 24-h pH monitoring. Intra-gastric pH data were nearly identical when the proton pump inhibitors were taken after meals. Even if the data were compared in different CYP2C19 genotypes, rabeprazole and esomeprazole did not show the difference. In poor metabolizer, both of the drugs showed stronger acid inhibition. When taken before meals, intra-gastric pH after esomeprazole administration was slightly but not significantly higher than that observed after rabeprazole administration not only in daytime but also in nighttime period. In conclusion, rabeprazole and esomeprazole were similarly effective when administered after a meal.

Calcium Carbonate Breath Test for Non-Invasive Estimation of Gastric Acid Secretion

Gastric acid measurement is useful in assessing the effectiveness of antisecretory drugs, however, the conventional tests involve invasive nasogastric intubation. Orally administered ¹³C-labeled calcium carbonate (Ca¹³CO₃) reacts with gastric acid to produce ¹³C-labeled carbon dioxide (¹³CO₂), which is then excreted in the breath. The objective of this study was to evaluate the suitability of Ca¹³CO3 breath test for estimating gastric acid secretion in human noninvasively. First, the Ca¹³CO₃ breath test and the measurement of pooled gastric acid under a fasting condition were performed in 6 healthy volunteers to evaluate the correlation between the two parameters. Next, endoscopic gastric acid collection and the Ca¹³CO₃ breath test were performed on different days after pentagastrin injection in 20 subjects to evaluate the correlation between the tests and the reproducibility. Finally, the same studies were repeated in 4 subjects before and after 1-week rabeprazole, a proton pump inhibitor, administration. The maximum CO₂ concentration (Cmax) correlated very well with the amount of pooled gastric acid (r = 0.95), suggesting that Ca¹³CO₃ breath test values well reflected the fasting intragastric acidity. The ¹³CO₂ concentration after pentagastrin injection correlated well with pentagastrin-stimulated maximal acid output (r = 0.79 at 20 min). The reproducibility of the Ca¹³CO₃ breath test under pentagastrin-stimulation was good (coefficient of variation = 0.11). Rabeprazole administration markedly reduced the values of the Ca¹³CO₃ breath test, suggesting that it can sensitively assess the efficacy of rabeprazole. The Ca¹³CO₃ breath test can potentially be a useful method for non-invasive estimation for gastric acid secretion in human.

Influence of the Meal and Genotype of CYP2C19 on the Pharmacokinetics of Proton Pump Inhibitors in Healthy Japanese Subjects

Objectives: To evaluate the influence of meals on the pharmacokinetics of omeprazole and rabeprazole and to investigate these PPIs with reference to CYP2C19 genotypes in healthy Japanese men. Methods: This was a randomized, open label, four-way crossover study. Twelve healthy Japanese male volunteers received a single oral dose of either 20 mg omeprazole or 10 mg rabeprazole, in the fasted state and after a standardized breakfast. Results: Between the administration of omeprazole in the fasted state and after breakfast, there were no significant differences in Cmax, AUC, Tmax, and half-life. Between the administration of rabeprazole in the fasted state and after breakfast, there were no significant differences in Cmax, AUC and half-life, whereas the Tmax of rabeprazole after breakfast was significantly delayed (2.8 ± 1.0 vs 5.3 ± 1.8 h, respectively; p = 0.006). PMs demonstrated the highest Cmax and AUC after drug intake under the fasting state and after breakfast, and homo EMs showed a significantly delayed Tmax. Conclusion: When a single dose of either PPI was administered, the pharmacokinetics of omeprazole was not affected by the meal, whereas the Tmax of rabeprazole after the meal was significantly delayed.

Response to Air Insufflation in Patients with Non-Erosive Gastro-Oesophageal Reflux Disease (NERD)

This study compared changes in intragastric pressure (IGP) in response to a gastric distension stimulus caused by air insufflation in 25 patients with non-erosive gastro-oesophageal reflux disease (NERD) and 34 healthy volunteers (controls). In four NERD patients, IGP responses were also measured before and after oral treatment with 10 mg rabeprazole daily for 2 weeks. The rate of increase in IGP at the start of insufflation was significantly higher in NERD patients than in controls. The time to appearance of symptoms (i.e. time to threshold) was significantly shorter in NERD patients than in controls. Direct measurement of IGP showed that visceral hypersensitivity and impaired fundal relaxation are both characteristic of NERD. Administration of rabeprazole led to a marked prolonging of time to threshold, indicating that treatment could alleviate this hypersensitivity.

Absence of Influence of Concomitant Administration of Rabeprazole on the Pharmacokinetics of Tacrolimus in Adult Living-donor Liver Transplant Patients: A Case–control Study

This study assesses the effects of rabeprazole on the pharmacokinetics of tacrolimus, considering the cytochrome P450 (CYP) 2C19 and CYP3A5 genotypes of living-donor liver transplant patients (native intestine) and their corresponding donors (graft liver). We examined the concentration/dose ratio of tacrolimus in transplant patients treated with (n=17) or without (n=38) rabeprazole at 10 mg/day on postoperative days 22-28. A stratified analysis revealed no significant differences between the control and rabeprazole groups in the median (range) concentration/dose ratio of tacrolimus [(ng/mL)/(mg/day)] for CYP2C19 extensive/intermediate metabolizers [2.71 (1.00-6.15) versus 2.55 (0.96-9.25); P=0.85] and for poor metabolizers [4.92 (2.44-7.00) versus 3.82 (2.00-7.31); P=0.68], respectively. Even based on the classification of CYP2C19 genotypes of donors, no significant difference in the concentration/dose ratio of tacrolimus was found for the two groups (CYP2C19 extensive/intermediate metabolizers, P=0.52; poor metabolizers, P=0.51). The same was observed for CYP3A5(*)1 carriers (P=0.97 for native intestine; P=0.87 for graft liver) and CYP3A5(*)3/(*)3 carriers (P=0.89 for native intestine; P=0.56 for graft liver). These findings suggest a safer dosing and monitoring of tacrolimus coadministered with rabeprazole early on after liver transplantation regardless of the CYP2C19 and CYP3A5 genotypes of transplant patients and their donors.

Significant Increase of Esophageal Mucin Secretion in Patients with Reflux Esophagitis After Healing with Rabeprazole: Its Esophagoprotective Potential

Esophageal mucin secretion in patients with reflux esophagitis (RE) is significantly impaired. Rabeprazole augments gastric mucin secretion. We have studied, therefore, the effect of rabeprazole on esophageal mucin secretion in patients with RE. The study was conducted in 15 patients with RE treated with rabeprazole (20 mg QD) for 8 weeks. Esophageal secretions were collected during consecutive infusions of initial NaCl, HCl/Pepsin (HCl/P), and a final NaCl, using a specially designed esophageal catheter, before and after therapy. Mucin was measured using standard methodology. After rabeprazole administration esophageal mucin concentration as well as secretion increased during perfusion with initial saline (P < 0.01), HCl/P (P < 0.02), and concluding saline (P < 0.001). Stimulation of esophageal mucin secretion by rabeprazole may indicate that the mechanisms governing its secretion are similar to those implicated in gastric mucin output. Enhancement of esophageal mucin secretion by rabeprazole may translate into esophagoprotective potential in patients with reflux esophagitis.

Influence of psychological intervention on life quality of patients with non-erosive reflux disease complicated with depression

Objective To study influence of psychological intervention on life quality of patients with non-erosive reflux disease(NERD) complicated with depression. Methods Patients with NERD and depression(95 cases) were divided randomly into the observation group(48 cases) and the control group(47 cases).The control group received oral administration of rabeprazole,10 mg,bid.The observation group was given psychological intervention based upon routine medication.Tbe reflux diagnostic questionnaire (RDQ), self-rating depression scale(SDS) and quality of life-index(QL-INDEX) scale were adopted for evaluation before and 8 weeks after treatment. Results The score of SDS was (41.58±6.85) in the observation group,which was lower than that of the control group,(50.42±9.26), after 8 weeks of treatment (P<0.01). The score of QL-INDEX was (8.56±1.38) in the observation group,which was higher than that of the con-trol group,(7.98±1.42), after 8 weeks of treatment (P<0.05). Conclusions Psychological intervention for patients with non-erosive reflux disease (NERD) complicated with depression can ameliorate their de-pression state and improve their life quality. Key words: Non-erosive reflux disease; Psychological intervention; Paroxetine; Depression; Life quality

Plasma concentration of rabeprazole after 8‐week administration in gastroesophageal reflux disease patients and intragastric pH elevation

The plasma concentration of rabeprazole in patients treated for gastroesophageal reflux disease (GERD) has not been reported, although the concentration in healthy volunteers has been reported previously. Here, CYP2C19 genotype effects of rabeprazole on the area under the plasma concentration-time curve (AUC) and the pH elevation were studied in GERD patients. Rabeprazole 10 mg/day was administrated for 8 weeks. AUC of rabeprazole in 18 Helicobacter pylori-negative GERD subjects (five CYP2C19 homozygous extensive metabolizers [homEM], eight heterozygous extensive metabolizers [hetEM] and five poor metabolizers [PM]) were determined after the final medication. Intragastric pH was recorded for 24 h at baseline and after the final medication. The AUC in the PM group (957 ng x h/mL) was significantly higher than those of homEM (375 ng x h/mL) and hetEM (542 ng x h/mL) groups. Median 24-h pH curves, median 24-h pH values and 24-h and nocturnal pH > 4 and pH > 3 holding times did not significantly differ among these groups. Disappearance of erosive lesions was observed after the treatment in all subjects with grade A, B or C at baseline irrespective of CYP2C19 genotypes. The AUC of rabeprazole depended on the CYP2C19 genotypes in Japanese GERD patients; however, the intragastric pH elevation was independent of CYP2C19 genotypes, which is consistent with the CYP2C19 genotype-independent healing efficacy of erosive lesions by rabeprazole. The present low AUC values indicated that abnormal accumulative effects on AUC did not occur during the period of the 8-week administration of rabeprazole.

No Relationship between Plasma Desacyl-Ghrelin Levels and Rabeprazole-Related Delay in Gastric Emptying

Recent studies have indicated that rabeprazole, a proton pump inhibitor, delays gastric emptying. However, the mechanism of action remains unclear. We conducted this study to clarify whether desacyl-ghrelin (the inactive form of the endogenous growth hormone secretagogue receptor ghrelin) is involved in rabeprazole-induced changes in gastric motor function. Twelve healthy males underwent (13)C-acetate breath tests to evaluate gastric emptying of a liquid meal twice after administration of rabeprazole 20 mg/day for 3 days or no medication (control). Gastric emptying was evaluated by two parameters: half-emptying time and time to peak (13)CO(2) excretion. Plasma desacyl-ghrelin levels were measured in blood samples collected at three time points: immediately pre-test and 1 and 2 hours after ingestion of the test meal. Rabeprazole significantly delayed gastric emptying of the liquid meal. However, plasma desacyl-ghrelin levels after ingestion of the liquid meal showed little difference before or after rabeprazole administration. The results indicate that desacyl-ghrelin was not associated with changes in gastric emptying caused by rabeprazole.

Subchronic toxicity and toxicokinetics of LZB, a new proton pump inhibitor, after 13-week repeated oral administration in dogs

The subchronic toxicity and toxicokinetics of a novel proton pump inhibitor, pymeprazole (LZB), were investigated in beagle dogs by daily oral administration for 13 consecutive weeks. Three test groups received doses of 30, 100 and 300 mg/kg/day of LZB. Rabeprazole of 60 mg/kg/day was used as positive control. The 13-week repeated oral doses of LZB resulted in objective signs of mild gastrointestinal disturbance for high-dose group animals. One individual dog of high-dose group was found to be lethargy and astasia at the last month of administration; for hematology, mild anemia was observed at high-dose females; for clinical chemistry, higher cholest, trigly and gastrin were observed at high-dose females, higher ASAT, ALAT, cholesterol, triglyceride and gastrin at high-dose males were also observed; for histopathology, the primary effects of LZB were related to gastric mucosa of high-dose group seen by H and E or Grimelius stain. Impairment of surface epithelium was observed by SEM. The treat-related effects basically were reversible for a 4-week drug-free period. As for positive control group, 13-week oral administration of rabeprazole resulted in more severe toxicity than high-dose group of LZB although much lower dose was employed. The accumulation of LZB after 13-week oral administration was not notable at the toxic dose of 300 mg/kg/day. The toxic dose was considered to be 100 mg/kg/day and the no-observed-adverse-effect level (NOAEL) to be 30 mg/kg/day, which is much higher than other PPIs. The toxicological target could be stomach, liver, hematological system and nervous system.

Monitoring Cytochrome P-450 Activity During Rabeprazole Treatment in Patients with Gastresophageal Reflux Disease

Proton pump inhibitors (PPIs) are the cornerstone in the treatment of gastresophageal reflux disease (GORD). PPIs are metabolized by the hepatic cytochrome P-450 enzymes (CYP-450). Rabeprazole is a PPI whose metabolism shows fewer interactions compared to other PPIs. In this study we evaluated the influence of rabeprazole administration on hepatic CYP-450 activity as measured by the (13)C-aminopyrine breath test ((13)C-ABT) in a group of patients with GORD. (13)C-ABT was performed on five GORD patients both before and after 1 week of rabeprazole administration (20 mg, b.i.d.). Pretreatment (13)C-ABT results were compared to posttreatment results. Pre- and posttreatment (13)C-ABT results for patients were compared to those obtained in five controls who did the test twice, with a 1-week interval in between. Before treatment, the (13)C-ABT results for the GORD patients did not significantly differ from those of healthy subjects. After treatment, we observed no significant modification of the (13)C-ABT in GORD patients compared to pretreatment values ((13)C-ABT %dose/hr, 10.56+/-1.31 versus 11.17+/-0.88; (13)C-ABT %cumulative dose, 8.08+/-1.11 versus 8.34+/-0.56). Posttreatment (13)C-ABT results were not significantly different from those obtained in controls at weekly repetition of the test. In patients with GORD, 1-week, full-dose rabeprazole does not display any significant interactions with CYP-450 activity.

Therapeutic effects of 10 mg/day rabeprazole administration on reflux esophagitis was not influenced by the CYP2C19 polymorphism

The acid suppressive effects of omeprazole (OPZ) and lansoprazole (LPZ) are influenced by the CYP2C19 polymorphism. On the other hand, some investigators have reported that acid suppressive effect of rabeprazole (RPZ) was not significantly affected by CYP2C19. The present study was designed to investigate whether the CYP2C19 genotype is related to the healing of reflux esophagitis (RE) in treatment with RPZ 10 mg. One hundred and three Japanese patients with RE were treated with daily oral administration of 10 mg RPZ. At 4 and 8 weeks after the start of treatment, healing of RE was evaluated endoscopically. The CYP2C19 genotype was investigated before the treatment. At 4 weeks after the start of treatment, the healing rates for homo-extensive metabolizer, hetero-extensive metabolizer, and poor metabolizer patients were 83.3% (15/18), 77.3% (17/22), and 88.9% (8/9) [corrected] respectively, and at 8 weeks after the start of treatment, the healing rates were 86.1% (31/36), 92.0% (46/50), and 82.4% (14/17), respectively. There were no significant differences in the healing rate of RE among the three genotypes at either 4 or 8 weeks after the start of treatment. The therapeutic effects of 10 mg/day RPZ administration on RE may be uninfluenced by the CYP2C19 polymorphism.