Nocturnal Acid Research Articles

Statistical Optimization and Fabrication of a Press Coated Pulsatile Dosage Form to Treat Nocturnal Acid Breakthrough

Present work focuses on the use of mimosa seed gum to develop a drug delivery system making combined use of floating and pulsatile principles, for the chrono-prevention of nocturnal acid breakthrough. The desired aim was achieved by fabricating a floating delivery system bearing time - lagged coating of Mimosa pudica seed polymer for the programmed release of Famotidine. Response Surface Methodology was the statistical tool that was employed for experiment designing, mathematical model generation and optimization study. A 3(2) full factorial design was used in designing the experiment.% weight ratio of mimosa gum to hydroxy propyl methyl cellulose in the coating combination and the coating weight were the independent variables, whereas the lag time and the cumulative % drug release in 360 minutes were the observed responses. Results revealed that both the coating composition and the coating weight significantly affected the release of drug from the dosage form. The optimized formulation prepared according to the computer generated software, Design-Expert(®) deciphered response which were in close proximity with the experimental responses, thus confirming the robustness as well as accuracy of the predicted model for the utilization of natural polymer like mimosa seed gum for the chronotherapeutic treatment of nocturnal acid breakthrough.

Relationships among rainfall, leaf hydrenchyma, and Crassulacean acid metabolism in Pyrrosia lanceolata (L.) Fraw. (Polypodiaceae) in central Taiwan

Leaf succulence is common among drought-adapted plants, including many tropical and subtropical epiphytic species. A prominent anatomical feature of many such succulent leaves is a clear, water-storing tissue often referred to as “hydrenchyma” (water-storage parenchyma). Functionally, hydrenchyma appears to store water for use by the leaf during drought. Although this has been confirmed in several laboratory studies, field studies linking the amount of hydrenchyma in plants with availability of water in their environment are lacking. In this study, the relative amount of leaf hydrenchyma in one of the most widely distributed epiphytes in Taiwan, Pyrrosia lanceolata, was measured in plants growing along a gradient of annual mean precipitation from 2048 to 3688mm. In addition, because Pyrrosia lanceolata is a Crassulacean acid metabolism (CAM) plant, the amount of CAM activity was also examined in plants along the gradient. At each of seven sites along the precipitation gradient, leaves were collected, and, using thin mid-leaf slices, the relative areas of the leaf cross-sections occupied by hydrenchyma were determined. CAM, measured as diel changes in leaf acidity, was measured in plants from each site in the field, after 3 days of water-saturation in the greenhouse, and also after 14 days without water in the greenhouse. Regressions of relative hydrenchyma with ten environmental variables in the dry season revealed that the amount of hydrenchyma was significantly and positively correlated with monthly mean number of rainless days, monthly mean number of days with daily mean temperature over 30°C, and monthly mean temperature. During the wet season, relative hydrenchyma area correlated only with the amount of cloud cover, and the correlation was negative. All plants at all sites exhibited CAM acid fluctuations in the field, under water-saturated conditions, and after desiccation. The largest nocturnal acid accumulations were found when plants were well-hydrated in the field and in the greenhouse, although evidence of drought-induced elevations of CAM was found at the drier sites. The results of this study indicate that the amount of leaf hydrenchyma was greatest in areas with warmer, drier environments. Also, drought-induced elevation of CAM activity occurred in plants from drier sites. This may help to explain the wide range of environments inhabited by this epiphytic fern in Taiwan.

Tu1830 Predictors of Slow Healing of Reflux Esophagitis With Potent Acid Suppression

Introduction: Proton pump inhibitors (PPIs) are now widely used for the treatment of acidrelated diseases, such as peptic ulcer and gastroesophageal reflux disease (GERD). PPIs which are weak-base prodrugs are activated in an acidic condition and only inhibit H+/K+ATPase that has already been activated. Therefore, the effect of PPIs on acid-related diseases is slow onset and their maximum efficacy can be achieved after several days of dosing, leading to unmet medical needs such as nocturnal acid breakthrough and unsatisfied symptom relief. Methods: We investigated the pharmacological profiles of YH4808, a novel potent, highly selective K+-competitive acid blocker (P-CAB), in terms of hog gastric H+/K+-ATPase activity, gastric acid secretion, and acute gastroesophageal lesions in animal models, in comparison with esomeprazole. In addition, a quantitative whole body autoradiography (QWBA) study was performed with [14C]YH4808 (10 mg/kg) in rats to characterize tissue distribution. Results: YH4808 inhibited H+/K+-ATPase activity in a concentration-dependent manner, with an IC50 value of 3.4 nM which is more potent than that of esomeprazole. The inhibitory mechanism of YH4808 on H+/K+-ATPase was a competitive antagonism to the K+-binding site of H+/K+-ATPase, and it was also a reversible inhibition. In a selectivity assay, YH4808 showed 3,000-fold greater selectivity against Na+/K+-ATPase. In pylorus-ligated rats, oral administration of YH4808 inhibited basal acid secretion in a dose-dependent manner with the ID50 value of 1.1 mg/kg. Anti-secretory activity of YH4808 against histamine-stimulated acid secretion in rats after IV injection (ID50=0.1 mg/kg) was stronger than that of esomeprazole (ID50=0.9 mg/kg). In Heidenhain pouch dogs, IV administration of YH4808 inhibited histamine-stimulated acid secretion in a dose-dependent manner with almost complete inhibition at the dose of 0.6 mg/kg. In a reflux esophagitis model, intraduodenal administration of YH4808 prevented esophageal lesions by 30, 82 and 91% at a dose of 1, 3, and 10 mg/kg, respectively while esomeprazole reduced the lesion by 47% at 10 mg/kg. A QWBA study in rats showed YH4808 accumulated and was retained in the gastric tissue for more than 24h after oral administration. Conclusion: YH4808, a novel selective P-CAB exerted a potent, longer-lasting anti-secretory efficacy through high accumulation in the gastric tissue, which translated into the more effective inhibition of reflux esophagitis than esomeprazole. These findings indicate that YH4808 can provide significant clinical benefits to patients with acid-related diseases.

Tu1827 Yh4808, a Potent, Highly Selective K+-Competitive Acid Blocker, Suppressed Rat Acute Reflux Esophagitis More Effectively Than Esomeprazole

Introduction: Proton pump inhibitors (PPIs) are now widely used for the treatment of acidrelated diseases, such as peptic ulcer and gastroesophageal reflux disease (GERD). PPIs which are weak-base prodrugs are activated in an acidic condition and only inhibit H+/K+ATPase that has already been activated. Therefore, the effect of PPIs on acid-related diseases is slow onset and their maximum efficacy can be achieved after several days of dosing, leading to unmet medical needs such as nocturnal acid breakthrough and unsatisfied symptom relief. Methods: We investigated the pharmacological profiles of YH4808, a novel potent, highly selective K+-competitive acid blocker (P-CAB), in terms of hog gastric H+/K+-ATPase activity, gastric acid secretion, and acute gastroesophageal lesions in animal models, in comparison with esomeprazole. In addition, a quantitative whole body autoradiography (QWBA) study was performed with [14C]YH4808 (10 mg/kg) in rats to characterize tissue distribution. Results: YH4808 inhibited H+/K+-ATPase activity in a concentration-dependent manner, with an IC50 value of 3.4 nM which is more potent than that of esomeprazole. The inhibitory mechanism of YH4808 on H+/K+-ATPase was a competitive antagonism to the K+-binding site of H+/K+-ATPase, and it was also a reversible inhibition. In a selectivity assay, YH4808 showed 3,000-fold greater selectivity against Na+/K+-ATPase. In pylorus-ligated rats, oral administration of YH4808 inhibited basal acid secretion in a dose-dependent manner with the ID50 value of 1.1 mg/kg. Anti-secretory activity of YH4808 against histamine-stimulated acid secretion in rats after IV injection (ID50=0.1 mg/kg) was stronger than that of esomeprazole (ID50=0.9 mg/kg). In Heidenhain pouch dogs, IV administration of YH4808 inhibited histamine-stimulated acid secretion in a dose-dependent manner with almost complete inhibition at the dose of 0.6 mg/kg. In a reflux esophagitis model, intraduodenal administration of YH4808 prevented esophageal lesions by 30, 82 and 91% at a dose of 1, 3, and 10 mg/kg, respectively while esomeprazole reduced the lesion by 47% at 10 mg/kg. A QWBA study in rats showed YH4808 accumulated and was retained in the gastric tissue for more than 24h after oral administration. Conclusion: YH4808, a novel selective P-CAB exerted a potent, longer-lasting anti-secretory efficacy through high accumulation in the gastric tissue, which translated into the more effective inhibition of reflux esophagitis than esomeprazole. These findings indicate that YH4808 can provide significant clinical benefits to patients with acid-related diseases.

Tu1828 Impact of Regurgitation on Health-Related Quality of Life (HRQoL) in Gastroesophageal Reflux Disease (GERD)

Introduction: Proton pump inhibitors (PPIs) are now widely used for the treatment of acidrelated diseases, such as peptic ulcer and gastroesophageal reflux disease (GERD). PPIs which are weak-base prodrugs are activated in an acidic condition and only inhibit H+/K+ATPase that has already been activated. Therefore, the effect of PPIs on acid-related diseases is slow onset and their maximum efficacy can be achieved after several days of dosing, leading to unmet medical needs such as nocturnal acid breakthrough and unsatisfied symptom relief. Methods: We investigated the pharmacological profiles of YH4808, a novel potent, highly selective K+-competitive acid blocker (P-CAB), in terms of hog gastric H+/K+-ATPase activity, gastric acid secretion, and acute gastroesophageal lesions in animal models, in comparison with esomeprazole. In addition, a quantitative whole body autoradiography (QWBA) study was performed with [14C]YH4808 (10 mg/kg) in rats to characterize tissue distribution. Results: YH4808 inhibited H+/K+-ATPase activity in a concentration-dependent manner, with an IC50 value of 3.4 nM which is more potent than that of esomeprazole. The inhibitory mechanism of YH4808 on H+/K+-ATPase was a competitive antagonism to the K+-binding site of H+/K+-ATPase, and it was also a reversible inhibition. In a selectivity assay, YH4808 showed 3,000-fold greater selectivity against Na+/K+-ATPase. In pylorus-ligated rats, oral administration of YH4808 inhibited basal acid secretion in a dose-dependent manner with the ID50 value of 1.1 mg/kg. Anti-secretory activity of YH4808 against histamine-stimulated acid secretion in rats after IV injection (ID50=0.1 mg/kg) was stronger than that of esomeprazole (ID50=0.9 mg/kg). In Heidenhain pouch dogs, IV administration of YH4808 inhibited histamine-stimulated acid secretion in a dose-dependent manner with almost complete inhibition at the dose of 0.6 mg/kg. In a reflux esophagitis model, intraduodenal administration of YH4808 prevented esophageal lesions by 30, 82 and 91% at a dose of 1, 3, and 10 mg/kg, respectively while esomeprazole reduced the lesion by 47% at 10 mg/kg. A QWBA study in rats showed YH4808 accumulated and was retained in the gastric tissue for more than 24h after oral administration. Conclusion: YH4808, a novel selective P-CAB exerted a potent, longer-lasting anti-secretory efficacy through high accumulation in the gastric tissue, which translated into the more effective inhibition of reflux esophagitis than esomeprazole. These findings indicate that YH4808 can provide significant clinical benefits to patients with acid-related diseases.

Abscisic acid and nitric oxide signaling in two different portions of detached leaves of Guzmania monostachia with CAM up-regulated by drought

Guzmania monostachia is an epiphyte tank bromeliad capable of up-regulating crassulacean acid metabolism (CAM) in response to several environmental stimuli, including drought and light stress. In other plant species, abscisic acid (ABA) and nitric oxide (NO) seem to be involved in CAM induction. Because the leaves of tank bromeliads perform different functions along their length, this study attempted to investigate whether ABA and NO are involved in regulation of CAM expression in this species by quantifying these compounds in apical and basal portions of the leaf, and whether there would be differences in this event for each leaf portion. Detached leaves exposed to a 30% polyethylene glycol solution showed a significant upregulation of CAM on the seventh day of treatment only in the apical portion, as indicated by nocturnal acid accumulation and phosphoenolpyruvate carboxylase (PEPC) activity. On the three days prior to CAM induction, ABA, NO and H2O2 were quantified. The amounts of ABA were higher in PEG-exposed leaves, along their entire length. NO, however, was higher only in the apical portion, precisely where CAM was up-regulated. H2O2 was higher only in the basal portion of PEG-exposed leaves. Our results suggest that ABA might be a systemic signal to drought, occurring in the entire leaf. NO and H2O2, however, may be signals restricted only to the apical or basal portions, respectively.

A novel once daily microparticulate dosage form comprising lansoprazole to prevent nocturnal acid breakthrough in the case of gastro-esophageal reflux disease: preparation, pharmacokinetic and pharmacodynamic evaluation

The objective of this study was to formulate and evaluate the lansoprazole (LPZ)-loaded microparticles to prevent nocturnal acid breakthrough in the case of gastro-esophageal reflux disease (GERD). The microparticulate delivery system was prepared by solvent evaporation method using Eudragit RS100 as a matrix polymer followed by enteric coated with Eudragit S100 and hydroxypropyl methylcellulose phthalate HP55 using spray drying method. The enteric coated microparticles were stable in gastric pH condition. In vivo pharmacokinetic and pharmacodynamic studies in male Wistar rats demonstrated that enteric coated microparticles sustained release of LPZ and promoted ulcer healing activity. In other words, the microparticulate dosage form provided effective drug concentration for a longer period as compared to conventional extended release dosage form, and showed sufficient anti-acid secretion activity to treat acid related disorders including the enrichment of nocturnal acid breakthrough event based on a once daily administration.

Effective therapy for nocturnal gastroesophageal acid reflux

Effective therapy for nocturnal gastroesophageal acid reflux

Association between nocturnal acid reflux and sleep disturbance

Association between nocturnal acid reflux and sleep disturbance

Design and Optimization of a Chronotherapeutic Dosage Form for Treatment of Nocturnal Acid Breakthrough

Present work focuses on the use of tamarind gum to develop a drug delivery system making combined use of floating and pulsatile principles, for the chrono-prevention of nocturnal acid breakthrough. The desired aim was achieved by fabricating a floating delivery system bearing time - lagged coating of Tamarindus indica seed polymer for the programmed release of Famotidine. Response Surface METHODology was the statistical tool that was employed for experiment designing, mathematical model generation and optimization study. A 32 full factorial design was used in designing the experiment. % weight ratio of tamarind gum to ethyl cellulose in the coating combination and the coating weight were the independent variables, whereas the lag time for drug release and the cumulative % drug release in 330 minutes were the observed responses. Results revealed that both the coating composition and the coating weight significantly affected the release of drug from the dosage form. The optimized formulation prepared according to the computer generated software, Design-Expert® deciphered response which were in close proximity with the experimental responses, thus confirming the robustness and accuracy of the predicted model for the utilization of natural polymer like tamarind gum for the chronotherapeutic treatment of nocturnal acid breakthrough.

Recent developments in gastroesophageal reflux disease and Barrett's esophagus: ANNO 2012

The incidence of gastroesophageal reflux disease (GERD) and esophageal columnar metaplasia is rising worldwide. Both mechanical and functional factors perturb the double sphincter barrier at the esophagogastric junction (EGJ). Discovery of the acid pocket is fundamental in understanding postprandial acid reflux. Adding impedencemetry to pH measurements allows detection of non-acid or weakly acidic reflux. Histologic and endoscopic injury of the squamous mucosa rises from dilation of the intercellular spaces, papillary extension, accentuated intrapapillary looping, red streaks, erosive tissue loss, etc., graded with the Los Angeles system. Seventy percent of patients have no recognizable abnormalities (non-erosive or neGERD). Treatment of GERD mainly relates to the control of acid secretion but a revival of alginate/antacid obliterating the acid pocket is to be expected. Weaker heartburn control in neGERD is a misnomer because most studies included patients with no evidence of reflux disease. Traditional (delayed-release) proton pump inhibitors (PPIs) are powerful suppressors of acid secretion but do have limitations such as gradual build up of acid control, weak control of nocturnal acid recovery, possibility of rebound, occasional need for dose escalation, etc. Barrett's esophagus (BE) is endoscopically diagnosed also in the absence of intestinal metaplasia. A prerequisite is the precise location of the EGJ (proximal end of gastric folds, esophageal sphincter pinch, distal extent of palisade vessels). BE is graded with the Prague C & M system. Barrett's cancer develops usually via low-grade and high-grade dysplasia. Endoscopic examination may indicate suspicious areas, amenable for targeted biopsy. Otherwise, four quadrant biopsies are obtained when searching for neoplasia. Low-grade dysplasia, especially when it is multifocal and p53 positive, high-grade dysplasia and mucosal cancer should be treated with endoscopic resection of the target area, followed by radiofrequency ablation of the adjacent non-neoplastic columnar mucosa, followed with powerful acid suppressant therapy. The long-term results of the combination of resection and ablation are exiting and at least comparable to surgical resection.

Gastroesophageal and laryngopharyngeal reflux profiles in patients with obstructive sleep apnea/hypopnea syndrome as determined by combined multichannel intraluminal impedance–pH monitoring

The profiles of gastroesophageal reflux (GER) and laryngopharyngeal reflux (LPR) in patients with obstructive sleep apnea/hypopnea syndrome (OSAHS) have never been explored. The aim of the study was to investigate the reflux profile in OSAHS patients. Consecutive snoring out-patients suspected with having OSAHS and 20 healthy volunteers were included. All subjects underwent simultaneous 24-h combined multichannel intraluminal impedance-pH (MII-pH) monitoring and polysomnography. Obstructive sleep apnea/hypopnea syndrome was defined when the apnea/hypopnea index was over 5. Stepwise multiple logistic regression analysis was performed to determine the predictor for OSAHS. Fifty-three patients were included, 37 with and 16 without OSAHS. The prevalence of reflux symptoms was similar between OSAHS (35.1%) and non-OSHAS (37.5%) patients. More OSAHS patients, compared with non-OSAHS patients and healthy volunteers, had pathologic acid GER, nocturnal acid GER, and prolonged acid clearance (P < 0.001). However, no difference in non-acid reflux episodes was observed among the three groups. Laryngopharyngeal reflux was detected in 51.4%, 43.8%, and 35.0% of OSAHS, non-OSAHS, and healthy volunteers, respectively (P = 0.034). In OSAHS patients, there was no difference in the sleep parameters between patients with and without LPR. Body mass index was the only predictor of OSAHS in the regression analysis. OSAHS patients have more pathologic acid GER and prolonged acid clearance than non-OSAHS patients whereas non-acid reflux was similar between the two groups. However, BMI, not GER, is the only independent predictor for OSAHS. Laryngopharyngeal reflux occurs in more than half of OSAHS patients despite no significant association with OSAHS.

Dose–response relationships of rabeprazole 5, 10, 20, and 40 mg once daily on suppression of gastric acid secretion through the night in healthy Japanese individuals with different CYP2C19 genotypes

This study was designed to investigate the antisecretory activity of rabeprazole administered once daily in doses of 5, 10, 20, and 40 mg and different cytochrome P450 2C19 (CYP2C19) genotypes on gastric pH in healthy individuals. Additional objectives were delineating the nighttime from the daytime effect and determining the relationships between the pharmacokinetics and pharmacodynamics of rabeprazole. Eight individuals of each of the three genotypes of CYP2C19-homozygous extensive metabolizers (homo-EMs), heterozygous EMs (hetero-EMs), and poor metabolizers (PMs)-were recruited. Twenty-four individuals received a once-daily dose, with dosing interval 24 h of 5, 10, 20, or 40 mg rabeprazole for 5 days in a 4-period crossover fashion. Twenty-four-hour intragastric pH and plasma rabeprazole concentrations were determined on day 5. A dose-dependent increase in median pH and in pH 4 holding time was observed across all CYP2C19 genotypes. When rabeprazole was increased from 20 mg to 40 mg, the differences and 95% confidence intervals (CIs) of nighttime pH 4 holding time between 40 mg and 20 mg in homo-EMs, hetero-EMs, and PMs were 8.0% (-5.0% -21.0%), 28.7% (15.7% -41.6%), and 16.9% (3.9% -29.9%), respectively. The relationship between the area under the plasma concentration-time curve up to the last time point at which rabeprazole was quantifiable (AUC(0-t)) and the pH 4 holding time could be described using a sigmoid maximum effect (E(max)) model. Our data demonstrate that increasing rabeprazole dose up to 40 mg once daily results in an increasing pharmacodynamic effect, which is most apparent for the control of nocturnal gastric acid secretion.

Barrett's esophagus: proton pump inhibitors and chemoprevention II

The following on proton pump inhibitors (PPIs) and chemoprevention in relation to Barrett's esophagus includes commentaries on 48-h pH monitoring, pH-impedence, bile acid testing, dyspepsia, long/short segment Barrett's esophagus, nonerosive reflux disease (NERD), functional heartburn, dual-release delivery PPIs, immediate-release PPIs, long-term PPI use, prokinetic agents, obesity, baclofen, nocturnal acid breakthrough, nonsteroidal anti-inflammatory drugs (NSAIDs), and new PPIs.

AN ASSOCIATION OF THE CLINICAL MANIFESTATIONS OF NSAID GASTROPATHY WITH UPPER GASTROINTESTINAL MOTOR DISORDERS IN PATIENTS WITH RHEUMATOID ARTHRITIS

Система комплексной поддержки и сопровождения научного журнала Elpub позволяет запустить двуязычный сайт журнала со встроенной системой электронной редакции в соответствии с лучшими издательскими практиками, а так же предусматривает техническую и методическую поддержку со стороны специалистов НЭИКОН.

Nocturnal Gastroesophageal Reflux: Assessment and Clinical Implications

Nocturnal Gastroesophageal Reflux: Assessment and Clinical Implications

Polysomnographic Diagnosed Sleep Disorders Are Associated With an Increased Incidence of Asymptomatic Nocturnal Acid Reflux

Polysomnographic Diagnosed Sleep Disorders Are Associated With an Increased Incidence of Asymptomatic Nocturnal Acid Reflux

Rabeprazole extended-release 50 mg compared with esomeprazole 40 mg and rabeprazole delayed release 20 mg

Rabeprazole extended-release 50 mg compared with esomeprazole 40 mg and rabeprazole delayed release 20 mg

DETERMINING THE OPTIMAL NIGHTTIME AIR TEMPERATURE FOR PHALAENOPSIS DURING THE VEGETATIVE STAGE

Daytime air temperatures above 26 degrees C inhibit flower initiation of Phalaenopsis regardless of the nighttime air temperature. This opens possibilities for energy saving by lowering the nighttime air temperature during the vegetative growth phase. As chilling injury can occur after a few hours exposure to cool temperature conditions, growers prefer to cultivate Phalaenopsis at daily temperatures between 25 and 30 degrees C. A better understanding of the low night temperature effects on the photosynthetic physiology of Phalaenopsis would improve production of these orchids in terms of greenhouse temperature control and energy use. Therefore, the Phalaenopsis hybrid 'Hercules' was subjected to nighttime air temperatures of 27.0, 24.0, 21.1, 18.0, 15.4 and 12.8 degrees C, while during the day temperatures of about 27.5 degrees C were maintained. Photoperiod was set to 9 h with non-saturating white fluorescent light (217.3 +/- 2.8 mu mol PAR m(-2) s(-1)). The chlorophyll fluorescence temperature response curves revealed a significant reduction of the photochemical quenching (qP) and quantum efficiency of PSII electron transport (Phi(PSII)) when plants were exposed to night temperatures below 21.1 degrees C, but maximum quantum yield of PSII photochemistry (F-v/F-m) suggested no PSII damage for these night temperatures. Early morning determined leaf acidity, which can be used as a measure of nocturnal malic acid production, and leaf water potential were lowest at night temperatures of 21.1 and 24.0 degrees C. However, maximum net CO2 uptake in the late night (2 h before daytime) was observed between 15.4 and 21.1 degrees C. Furthermore, PSII photochemistry required only 5 h for full recovery of all night temperatures imposed. Our results suggest that Phalaenopsis can tolerate relatively cool night temperatures during the vegetative growth stage.

Pantoprazole Induced Elevation of Transaminases: A Case Report and Literature Review

Purpose: Case Report: An 88-year-old female was treated for infectious colitis. On admission, the transaminases, alkaline phosphatase and total bilirubin were normal. On Day 2 of hospitalization she was started empirically on oral pantoprazole for a history of peptic ulcer disease. By Day 4 the transaminases were noted to be increasing. Viral and autoimmune hepatitis evaluations were negative. There was no hypotension. Ultrasound of the liver was normal. The only potentially hepatotoxic agents were pantoprazole, simvastatin and metoprolol. The pantoprazole was stopped on Day 6 and the other medications were continued. The transaminases began to normalize. Discussion: PPI are a substituted benzimidazole that inhibits gastric acid secretion by interference with proton pumps on the secretory membrane of parietal cells. Compounds containing benzimidazole are metabolized by CYP2C19. Polymorphisms of the gene result in 3 distinct phenotypes. These are homozygous extensive metabolizer (homEM), heterozygous extensive metabolizer (hetEM) and poor metabolizer (PM). The plasma level of omeprazole is sustained for much longer in PM and can be as high as the peak concentration in persons who are homEM. In addition, the area under the curve for PM may be 13 times as high at homEM. Patients with GERD positive for mucosal breaks were treated for 8 weeks with 30 mg of lansoprazole. Cure rates based on endoscopy were lowest in homoEM followed by heteEM. The PM group was highest due to high plasma lansoprazole levels and less frequent nocturnal acid breakthrough (NAB). Higher doses of PPI are required for treatment and maintenance. Reported long term effect of PPI on human body includes increased gastrin level, megaloblastic anemia and atrophic gastritis. In children, long term use of PPI is safe and well tolerated. Hepatitis has been seen in several PPI. In a report of fulminant hepatic failure post mortem examination of the liver demonstrated massive central zone necrosis (5,9). Some elecations of transaminases are benign and have been reported in <1% of all patients taking omeprazole. Most elevations returned to normal in a few days and all returned to normal after 6 weeks. In the non-ICU setting, there is widespread use of PPI for stress ulcer prophylaxis or GI prophylaxis, on the basis of potential adverse effects and substantial health care cost the inappropriate use of PPI should be discouraged.