Optimal dose of intravenous pantoprazole in patients with peptic ulcer bleeding requiring endoscopic hemostasis in Korea

Background and Aim:  The lowest effective dose of proton pump inhibitors (PPI) for prevention of peptic ulcer rebleeding remains unclear. The objective of the present study was to evaluate whether low-dose PPI has a similar efficacy to high-dose i.v. administration for maintaining intragastric pH above 6.
Methods:  Sixty-one patients with bleeding ulcers were randomized into one of three groups after endoscopic hemostasis: pantoprazole 80 mg bolus followed by 8 mg/h; 40 mg, 4 mg/h infusion; and bolus injection of 40 mg every 24 h. Intragastric pH values and rebleeding rates were measured. In addition, pharmacokinetic parameters and association with CYP2C19 polymorphisms and H. pylori infection were assessed.
Results:  Mean percentage of time with intragastric pH > 6, and the proportion of patients with pH > 6 for more than 60% of the time were significantly higher in the 40 mg, 4 mg/h infusion group compared to the 40 mg bolus injection. There was no significant difference between the 80 mg, 8 mg/h and the 40 mg, 4 mg/h groups. In the H. pylori (−) group, only 40% of patients that received continuous infusion reached the target pH > 6 for more than 60% of the time; this was significantly lower than the H. pylori (+) group, 87.5% ( P  = 0.026).
Conclusions:  A continuous infusion, regardless of high or low dose, was more effective for acid suppression than a 40 mg bolus PPI injection in Korea. H. pylori infection was an important factor for the maintenance of an intragastric pH > 6.     

Effect of intravenous application of esomeprazole 40 mg versus pantoprazole 40 mg on 24-hour intragastric pH in healthy adults

BACKGROUND: It has been demonstrated that therapy with proton pump inhibitors reduces recurrence of bleeding following initial endoscopic treatment of bleeding peptic ulcers. AIM: This study compared the effects of esomeprazole 40 mg and pantoprazole 40 mg on intragastric acid control. Both substances were administered intravenously as 15-min infusion and as bolus injection. METHODS: Healthy men and women volunteers were enrolled in this single-center, open, randomized, three-way crossover study. After administration of esomeprazole 40 mg and pantoprazole 40 mg intravenously as 15-min infusion, and pantoprazole 40 mg intravenously as bolus injection, continuous 24-h intragastric pH monitoring was carried out. RESULTS: pH data were available for 21 Helicobacter pylori-negative and seven H. pylori-positive volunteers. In H. pylori-negative volunteers, esomeprazole 40 mg intravenously resulted in 11.8 h with an intragastric pH>4 compared with 5.6 h for pantoprazole 40 mg intravenously as infusion (P<0.0001), and 7.2 h for pantoprazole 40 mg intravenously as bolus injection (P<0.001). During the first 6 h of administration, the corresponding values were 3.4, 1.1 (P<0.000001), and 2.1 h (P<0.001), respectively. CONCLUSIONS: In H. pylori-negative patients, a single dose of esomeprazole 40 mg intravenously provides an intragastric acid control that is faster and more pronounced than administration of pantoprazole 40 mg intravenously.     

Combinations containing amoxicillin-clavulanate and tetracycline are inappropriate for Helicobacter pylori eradication despite high in vitro susceptibility

BACKGROUND: The purpose of the present paper was to evaluate the efficacy and tolerability of amoxicillin-clavulanate and tetracycline-based quadruple therapy as an alternative second-line treatment for H. pylori infection. METHODS: The study subjects consisted of 54 patients infected with H. pylori, in whom initial triple therapy had failed. Subjects were randomized to receive the following 7-day therapies: (i) pantoprazole 40 mg b.i.d., tripotassium dicitrate bismuthate 300 mg q.i.d., amoxicillin-clavulanate 1000 mg b.i.d., and tetracycline 500 mg q.i.d. (PBAT); or (ii) pantoprazole 40 mg b.i.d., tripotassium dicitrate bismuthate 300 mg q.i.d., metronidazole 500 mg t.i.d., and tetracycline 500 mg q.i.d. (PBMT). Eradication rates based on antibiotic susceptibility, drug compliance and side-effect rates were evaluated and compared. RESULTS: The H. pylori eradication rates were 16.0%/17.4% with PBAT and 65.5%/70.4% with PBMT by intention-to-treat (P<0.001) and per-protocol analyses (P<0.001), respectively. In patients who received PBAT, the eradication rates were only 16.7% (2/12) for both amoxicillin and tetracycline-susceptible H. pylori strains. Drug compliance and side-effect rates were similar in the two groups. CONCLUSIONS: Despite high individual in vitro antimicrobial activity, amoxicillin-clavulanate and tetracycline-based quadruple therapy showed low eradication rates, which strongly suggests that it should not be considered as a therapeutic option for H. pylori eradication.     

Acid-suppressive effects of rabeprazole: Comparing 10 mg and 20 mg twice daily in Japanese Helicobacter pylori-negative and -positive CYP2C19 extensive metabolisers

BACKGROUND: Rabeprazole 10mg b.i.d. is often administered as therapy for eradication of Helicobacter pylori (H. pylori) and is also proposed as therapy for refractory gastro-oesophageal reflux disease. However, there has not been a comprehensive assessment of its acid-suppressive effects. AIMS: To compare the acid-suppressive effects of rabeprazole 10mg b.i.d. with 20mg b.i.d. considering H. pylori status. SUBJECTS: Thirteen H. pylori-negative and eleven H. pylori-positive Japanese CYP2C19 extensive metabolisers (<35 years). METHODS: Intragastric pH was measured for 24h three times in a randomised manner; on day 7 of the repeated administration of rabeprazole 10mg b.i.d. or 20mg b.i.d., or a placebo. RESULTS: In median intragastric pH value and percent time of pH>3.0, >4.0, >5.0, >6.0, and >7.0 for 24h, no significant differences were observed between the two doses in either H. pylori-negative or H. pylori-positive subjects. At either dose, these parameters were significantly higher in H. pylori-positive subjects than in H. pylori-negative subjects. Nocturnal acid breakthrough occurred in seven and two of the thirteen H. pylori-negative subjects and one and two of the eleven H. pylori-positive subjects at each dose, respectively. CONCLUSIONS: The effects of rabeprazole 10mg b.i.d. were equal to those of 20mg b.i.d. in H. pylori-positive subjects; whereas in H. pylori-negative subjects, 20mg b.i.d. was superior for prevention of nocturnal acid breakthrough.     

Effects of CYP2C19 and MDR1 genotype on the eradication rate of Helicobacter pylori infection by triple therapy with pantoprazole, amoxycillin and clarithromycin

Backgrounds:  CYP2C19 polymorphism plays an important role in the metabolism of proton pump inhibitors. The multidrug resistance (MDR)1 genotype is associated with the successful eradication of Helicobacter pylori . The aim of the present study was to investigate the effects of CYP2C19 and MDR1 genotypes on the eradication rate of H. pylori using a pantoprazole-based triple therapy.
Methods:  A total of 210 patients infected with H. pylori were treated with 40 mg pantoprazole, 500 mg clarithromycin and 1000 mg amoxicillin twice daily for 7 days. The CYP2C19 genotype was determined with polymerase chain reaction (PCR)–restriction fragment length polymorphism analysis. The MDR1 C3435T polymorphism was identified by PCR-based allele-specific amplification (PCR-ASA).
Results:  Of the 210 patients who completed the study, 174 (82.9%, 95.0% confidence interval [CI], 77.8–88.0%) achieved successful eradication after the first cycle of therapy. The eradication rates for H. pylori were 86.7%, 81.1% and 82.1% in the homozygous extensive, heterozygous extensive and poor metabolizer groups, respectively ( P  = 0.65). Moreover, the cure rates in the CC, CT, and TT groups were 82.7%, 84.4% and 76.9%, respectively ( P  = 0.66). Multiple logistic regression analysis revealed that endoscopic diagnosis was a significant independent risk factor for treatment failure.
Conclusion:  The eradication rates of H. pylori by pantoprazole, amoxicillin and clarithromycin were not significantly different among the CYP2C19 and MDR1 genotypes. Hence, the cure rate of H. pylori in the Korean population was no different for the CYP2C19 and MDR1 genotypes.     

Influence of CYP2C19 polymorphism and Helicobacter pylori status on the antisecretory effect of omeprazole in gastroesophageal reflux disease]

BACKGROUND/AIMS: The acid suppressive effect of omeprazole (OMP) is influenced by the metabolic capacity of gastric acid suppression, which is dependent on CYP2C19 polymorphism. The aim of this study was to determine the influence of CYP2C19 polymorphism and Helicobacter pylori (H. pylori) infection on the intragastric acid suppression of OMP. METHODS: Thirty one patients with gastroesophageal reflux disease were treated with a daily oral dose of 20 mg OMP for 28 days. Patients were genotyped for CYP2C19 polymorphism by polymerase chain reaction-restriction fragment length polymorphism and classified into three groups: homogenous extensive metabolizers (Ho-EMs), heterogenous extensive metabolizers (Ht-EMs) and poor metabolizer (PMs). H. pylori infection status were assessed before OMP treatment. Intragastric pH was monitored over twenty four-hours before (day 0) and after (day 29) the treatment with OMP. RESULTS: Twenty four-hour intragastric mean pH in the PMs group was significantly higher than those in Ho-EMs and Ht-EMs (5.3+/-1.3 vs. 2.8+/-0.6, 3.6+/-1.4) (p<0.005). Twenty four-hour intragastric mean pH after the administration of OMP in the H. pylori positive group was significantly higher than the H. pylori negative group (4.7+/-1.4 vs. 3.2+/-1.4) (p<0.001). There was no significant difference in acid suppressive activity of OMP between H. pylori positive and negative group according to CYP2C19 polymorphism. CONCLUSIONS: The acid suppressive effect of OMP on intragastric pH is dependent on CYP2C19 polymorphism and the H. pylori-infected status in patients with gastroesophageal reflux disease. H. pylori infection may play a role in enhancing the acid suppressive potential of OMP.     

非静脉曲张性上消化道出血患者胃内酸性水平和CYP2C19基因多态性与奥美拉唑给药方式关系

[目的]探究奥美拉唑(OME)在胃内酸性水平和细胞色素P450 2C19(CYP2C19)基因型和表型等因素影响下的最佳应用方法。[方法]对非静脉曲张性上消化道出血(NVUGIB)患者进行前瞻性研究。2015年3月~2018年12月收集分析了110例样本,其中包括48例OME静脉滴注给药和62例OME静脉注射给药患者。在内镜下止血术后,静脉滴注组给予80 mg OME静脉注射,之后OME静脉滴注组用8 mg/h OME连续静脉滴注72 h;静脉注射组在给予80 mg OME静脉注射后5 min内再每12 h接受40 mg OME静脉注射。在此过程中记录胃内酸性水平,分析CYP2C19变异等位基因(*2,*3,*17),测定血清中OME和5-羟奥美拉唑(5-OH-OME)的浓度。[结果]①OME给药方式与胃内pH值持续的不同时间段关系:2组胃内pH值>4和>6在0~12 h内均无明显区别。2组胃内pH值>4在0~48 h(滴注组vs.注射组,100.0%vs.96.8%,P=0.031)以及0~72 h(滴注组vs.注射组,100.0%vs.87.5%,P=0.001)差异有统计学意义。2组胃内pH值>6在0~72 h内(滴注组vs.注射组,97.4%vs.64.1%,P=0.036)差异有统计学意义。②OME给药方式与是否感染幽门螺杆菌(Hp)的关系:与未感染的患者相比,滴注组Hp感染患者的胃内pH值20 min(6.2 vs.4.8,P=0.16);40 min(6.5 vs.6.0,P=0.023);60 min(6.9 vs.6.3,P=0.009)更高。滴注组Hp感染患者的胃内pH值在给药后0 min^6 h增长(1.5vs.7.6,P=0.012)最大。但注射组在pH值>4和>6的平均时间百分比以及在不同给药时间上差异无统计学意义。③OME给药方式与CYP2C19基因型和表型的关系:在不同CYP2C19等位基因变异类型中,滴注组UM比EM更快使胃内pH值达到>6(P>0.05),而注射组EM似乎比UM更有效(P>0.05)。且给药方式与CYP2C19变异等位基因(*2,*3,*17)多态性无关。[结论]在NVUGIB患者中,无论CYP2C19基因多态性如何,OME单次注射治疗后,持续滴注给药比每12 h 1次注射给药在保持较高的胃内pH值中更有效。Hp感染可加速胃内pH的初始升高。     

Randomized study of two "rescue" therapies for Helicobacter pylori-infected patients after failure of standard triple therapies

OBJECTIVES: A novel rifabutin-based therapy is able to cure Helicobacter pylori infection in most patients who have failed eradication after standard proton pump inhibitor (PPI)-based triple therapy. We compared this regimen with the quadruple therapy. METHODS: A total of 135 patients were randomized into three groups who were treated for 10 days with pantoprazole 40 mg b.i.d., amoxycillin 1 g b.i.d., and rifabutin 150 mg o.d. (RAP50150 group), or 300 mg o.d. (RAP300 group), and pantoprazole 40 mg b.i.d., metronidazole 250 mg t.i.d., bismuth citrate 240 mg b.i.d., and tetracycline 500 mg q.i.d. (QT group). Before therapy, patients underwent endoscopy with biopsies for histology, culture and antibiotic susceptibility tests. H. pylori eradication was assessed by the 13C-urea breath test. RESULTS: On intention-to-treat analysis, eradication rates (with 95% confidence intervals [CI]) were 66.6% (53-80%) in the RAP150 and QT groups, respectively, and 86.6% (76-96%) in RAP300 group (p < 0.025). Most patients harboring metronidazole- and clarithromycin-resistant strains were eradicated at an equal rate by each of the three regimens. Side effects were observed in 9% and 11% of rifabutin-treated patients, and in 47% of those on quadruple therapy (p < 0.0001). CONCLUSIONS: In patients who failed standard eradicating treatments, a 10-day course of rifabutin with pantoprazole and amoxycillin is more effective and well tolerated than the quadruple therapy.     

Comparison of p.o. or i.v. proton pump inhibitors on 72-h intragastric pH in bleeding peptic ulcer

Background and Aims:  After successful endoscopic hemostasis in bleeding peptic ulcer, addition of proton pump inhibitors reduce the rate of recurrent bleeding by maintaining intragastric pH at neutral level. The aim of the present study was to evaluate the effect of various proton pump inhibitors given through different routes on intragastric pH over 72 h after endoscopic hemostasis in bleeding peptic ulcer.
Methods:  Ninety consecutive patients who had successful endoscopic therapy of bleeding peptic ulcer underwent 72-h continuous ambulatory intragastric pH study, were randomly assigned to receive p.o. omeprazole 80 mg bolus followed by 40 mg every 12 h for 72 h or i.v. 80 mg omeprazole followed by infusion 8 mg/h for 72 h. Oral pantoprazole 80 mg bolus followed by 80 mg every 12 h for 72 h or i.v. 80 mg pantoprazole followed by infusion of 8 mg/h for 72 h. Oral rabeprazole 80 mg bolus followed by 40 mg every 12 h for 72 h or i.v. 80 mg rabeprazole followed by infusion 8 mg/h for 72 h. Five patients received no treatment after successful endoscopic therapy and underwent 72-h pH study.
Results:  Mean 72-h intragastric pH for p.o. omeprazole was 6.56 versus 6.93 for omeprazole infusion ( P  = 0.48). Mean 72-h intragastric pH for p.o. pantoprazole was 6.34 versus 6.32 for pantoprazole infusion ( P  = 0.62). Mean 72-h intragastric pH for rabeprazole p.o. was 6.11 versus 6.18 rabeprazole i.v. ( P  = 0.55). Mean 72-h pH for the no proton pump inhibitor group was 2.04.
Conclusion:  There was no significant difference among various proton pump inhibitors given through different routes on raising intragastric pH above 6 for 72 h after successful endoscopic hemostasis in bleeding peptic ulcer.     

Oral buffered esomeprazole is superior to i.v. pantoprazole for rapid rise of intragastric pH: A wireless pH metry analysis

Background and Aims:  A pH of more than 6 is required for clot stability and hemostasis. Intravenous proton pump inhibitors have a rapid onset of action compared to oral and have been preferred for management of non-variceal bleeding. Intravenous pantoprazole has been used extensively. Buffered esomeprazole (BE) is an oral preparation consisting of an inner core of non-enteric-coated esomeprazole with a shell of sodium bicarbonate. The buffer protects against acid degradation of esomeprazole in addition to immediate antacid action. The aim of this study was to assess the efficacy of BE for raising and maintaining an intragastric pH of more than 6 in comparison to i.v. pantoprazole in equivalent dosing.
Methods:  A randomized two-way cross-over study was conducted. Ten healthy volunteers were randomized to twice daily BE 40 mg or pantoprazole 40 mg i.v. bolus. Intragastric pH was measured with a wireless pH radiotelemetry capsule (Bravo, Medtronic). A 2-week washout period was given between doses.
Results:  BE achieved a steady pH of more than 6 in a median time of 2 min (range 1–5 min) after the first dose. The mean % time that intragastric pH was more than 6.0 for BE was 96%, and 90% of the 24-h period compared to pantoprazole (47% and 18%), P  = 0.000. A median pH (interquartile range) for the BE group was 6.2 (6.175–6.2) which was higher than i.v. pantoprazole 4.60 (4.5–5.0) ( P  = 0.005).
Conclusion:  BE achieves and maintains a pH of more than 6 within minutes of administration. It was significantly superior to i.v. pantoprazole in equivalent dosing. This finding could have implications in the management of non-variceal bleed where a rapid and sustained pH of more than 6 is desirable.     

Recent success of pantoprazole -or lansoprazole- based clarithromycin plus amoxicillin treatment in the eradication of Helicobacter pylori.

BACKGROUND/AIMS: There are some reports showing that resistance of Helicobacter pylori (H. pylori) to clarithromycin has increased in recent years. We aimed to investigate the current success of a most popular first-line eradication regimen by using two different proton pump inhibitors: lansoprazole and pantoprazole. METHODS: Ninety patients with H. pylori-positive functional dyspepsia were randomized to receive pantoprazole 40 mg b.i.d. or lansoprazole 30 mg b.i.d. in addition to amoxicillin 1,000 mg and clarithromycin 500 mg twice daily for 14 days in a multicenter study. H. pylori infection was determined by histological examination and a rapid urease test. A follow-up endoscopy was performed to assess the H. pylori eradication six weeks after the end of therapy. RESULTS: Seventy-nine patients completed the study protocol properly. The H. pylori eradication rates according to per protocol analysis were 70% in group pantoprazole, amoxicillin and clarithromycin (28/40) and 69.2% in group pantoprazole, amoxicillin and clarithromycin (27/39). The eradication rates according to intention to treat analysis were 62.2% and 60% in lansoprazole, amoxicillin, clarithromycin, pantoprazole, amoxicillin, clarithromycin groups, respectively. The eradication rates were similar in both protocols (p>0.05). CONCLUSIONS: The most popular first-line eradication protocols of H. pylori achieved only a moderate success in the current study. Alternative therapy options are needed instead of clarithromycin-based triple treatment for eradication of H. pylori. The choice of proton pump inhibitor is not important in the eradication rate of H. pylori.     

Randomized open trial for comparison of proton pump inhibitors in triple therapy for Helicobacter pylori infection in relation to CYP2C19 genotype

BACKGROUND AND AIMS: Genetic polymorphism of cytochrome P450 (CYP) 2C19 influences the efficacy of Helicobacter pylori eradication therapy with a proton pump inhibitor (PPI) and amoxicillin. However, in triple therapy (PPI plus amoxicillin and clarithromycin), little is known about the impact of CYP2C19 polymorphism, or the use of rabeprazole, which is not well metabolized by CYP2C19. The efficacy of three PPI (omeprazole, lansoprazole, and rabeprazole) in a 1-week triple regimen were compared in relation to CYP2C19 polymorphism. METHOD: One hundred and eighty-three patients were randomized to receive one of the following regimens: amoxicillin 500 mg t.i.d., clarithromycin 200 mg t.i.d., and PPI (omeprazole 20 mg, lansoprazole 30 mg, or rabeprazole 10 mg) b.i.d. CYP2C19 polymorphism was analyzed by PCR restriction fragment length polymorphism. RESULTS: Intention-to-treat-based overall cure rates for omeprazole, lansoprazole or rabeprazole regimens were 83.1% (95% confidence interval (CI): 69-89%), 86.7% (CI: 75-93%), and 76.6% (CI: 64-85%), respectively, without significant difference. The cure rate of the rabeprazole regimen (but not the lansoprazole or omeprazole regimens) tended to be correlated with CYP2C19 genotypes (P = 0.076). In patients with a homozygous extensive metabolizer genotype, the per protocol-based cure rate with rabeprazole (62.5%) was significantly lower than that with lansoprazole (90.0%; P = 0.038). CONCLUSION: The overall cure rate of 1-week triple therapy for H. pylori eradication was not significantly different between regimens with omeprazole, lansoprazole or rabeprazole, but the impact of CYP2C19 genetic polymorphism on the cure rate appeared to differ between these PPI.     

Cure of Helicobacter pylori infection and healing of duodenal ulcer: comparison of pantoprazole-based one-week modified triple therapy versus two-week dual therapy

Objective: Eradication of Helicobacter pylori ( H. pylori ) is recommended as the first-line therapeutic concept for reliable long-term prevention of duodenal ulcer (DU) relapse. Current treatment regimens vary in efficacy, complexity, and compliance. To assess the efficacy of pantoprazole in H. pylori eradication in parallel groups of patients using two eradication regimens.
Methods: Patients, (18–85 yr old; intention-to-treat,  n = 286  ) with proven DU, positive rapid urease test (biopsy), and ¹³C-urea breath test (UBT) were included in a prospective, randomized, multicenter study. Modified triple therapy consisted of 40 mg pantoprazole b.i.d ., 500 mg clarithromycin t.i.d ., and 500 mg metronidazole t.i.d . for 7 days (PCM therapy); dual therapy consisted of 40 mg pantoprazole b.i.d . and 500 mg clarithromycin t.i.d . for 14 days (PC therapy). In both groups 40 mg pantoprazole o.d . was given until day 28 when healing of DU was evaluated endoscopically; H. pylori status was assessed by UBT on day 56.
Results: H. pylori eradication rate was 95% in PCM versus 60% in PC therapy groups (per-protocol population,   p < 0.001  ), and 82% in PCM versus 50% in PC therapy in the intention-to-treat patient population (   p < 0.001  ). The DU healing rate was 98% in the PCM and 95% in the PC therapy groups (per-protocol population). Both regimens were similarly well tolerated. Adverse events in both regimens included taste disturbance, diarrhea, and increased serum concentration of liver enzymes, at an incidence of < 10%.
Conclusions: Compared to 2-wk PC therapy (pantoprazole and clarithromycin), the 1-wk PCM therapy (pantoprazole, clarithromycin, and metronidazole) is a significantly superior and highly promising strategy for eradication of H. pylori .     

不同细胞色素P4502C19基因型肝病合并消化性溃疡患者泮托拉唑钠血药浓度测定

细胞色素P4502C19（CYP2C19）基因多态性对第一代质子泵抑制剂（PPI）的代谢有直接影响。CYP2C19的表达具有肝脏特异性。目的：观察不同CYP2C19基因型肝病合并消化性溃疡患者泮托拉唑钠代谢的差异，探讨肝脏病变对CYP2C19活性的影响。方法：合并消化性溃疡的2l例原发性肝癌患者和22例脂肪肝患者纳入研究，25名健康志愿者作为对照。受试者口服泮托拉唑钠40mg／d一周，分别于服药ld和7d后采血，以反相高效液相色谱法测定血浆泮托拉唑钠浓度。结果：服药7d后，健康对照组、脂肪肝组和原发性肝癌组CYP2C19强代谢者的血浆泮托拉唑钠浓度均显著低于弱代谢者（P〈0．05）。无论是强代谢者还是弱代谢者，服药7d后血浆泮托拉唑钠浓度均表现为原发性肝癌组〉脂肪肝组〉健康对照组（P〈O．05）。结论：CYP2C19活性与肝病严重程度呈负相关。终末期肝病患者泮托拉唑钠血药浓度明显升高，尤其是CYP2C19弱代谢者。     

Blood concentration of pantoprazole sodium is significantly high in hepatogenic peptic ulcer patients,especially those with a poor CYP2C19 metabolism

OBJECTIVE: To determine the plasma concentration of pantoprazole sodium by high performance liquid chromatography and its distribution in patients with different CYP2C19 genotypes in an attempt to provide experimental data for the clinical dosage adjustment of the drug. METHODS: Patients with liver disease and associated peptic ulcer were genotyped according to their CYP2C19 wild‐type sequences and mutations in CYP2C19m1 and CYP2C19m2 by the principles of the American Surgical Association using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). The plasma concentration of pantoprazole sodium was detected after oral administration of the enteric‐coated capsules in all patients. Included in the present study were 21 patients with primary liver cancer complicated by pathogenic peptic ulcers (confirmed by endoscopy), 22 patients with fatty liver and 25 healthy volunteers between January 2006 and October 2007. The subjects were administered orally with pantoprazole sodium at 40 mg/day for 1 week consecutively. The drug concentration was detected at 24 h and 1 week after drug administration by drawing 3.0 mL blood from the cubital vein. RESULTS: The plasma concentration of pantoprazole sodium was related to the CYP2C19 enzyme type. The plasma concentration of extensive metabolizers (EM) was lower than that of poor metabolizers (PM) in the healthy control group at day 7 of drug administration. Regardless of PM or EM, the plasma concentration of pantoprazole sodium in primary liver cancer patients was higher than that in fatty liver patients, and even higher than that in healthy controls (P < 0.05). CONCLUSION: These results suggest that CYP2C19 activity is inversely correlated with the severity of liver disease, especially in PM patients.     

Symptom relief in gastroesophageal reflux disease: a randomized, controlled comparison of pantoprazole and nizatidine in a mixed patient population with erosive esophagitis or endoscopy-negative reflux disease.

OBJECTIVES: Gastroesophageal reflux disease (GERD) in primary care practice presents symptomatically, and resources to distinguish promptly between erosive esophagitis and endoscopy-negative reflux disease (ENRD) are limited. It is therefore important to determine the roles of proton pump inhibitors and histamine-2-receptor antagonists for first-line symptom-based therapy in patients with erosive esophagitis and ENRD. The aim of this study was to compare pantoprazole 40 mg once daily versus nizatidine 150 mg b.i.d. in a mixed GERD patient population with ENRD or erosive esophagitis (Savary-Miller grades 1-3). METHODS: A 4-wk randomized, double-blind, parallel-group, multicenter study conducted in Canada. Eligible patients had experienced GERD symptoms > or = 4 times weekly for > 6 months. Patients were randomized to pantoprazole 40 mg once daily or nizatidine 150 mg b.i.d.. Endoscopy was performed before randomization and after 4 wk of therapy. RESULTS: Of 220 patients randomized to therapy, 208 were available for a modified intent-to-treat analysis. Erosive esophagitis was present in 125 patients; 35 patients were Helicobacter pylori positive. There was complete symptom relief after 7 days of therapy in 14% of patients on nizatidine and in 40% of those on pantoprazole (p < 0.0001), and after 28 days of treatment in 36% and 63% of patients, respectively (p < 0.0001). After 28 days of treatment, adequate heartburn control was reported by 58% of the nizatidine group and in 88% of the pantoprazole (p < 0.0001); erosive esophagitis healing rates were 44% for nizatidine and 79% for pantoprazole (p < 0.001). Rescue antacid was needed by a greater number of patients using nizatidine than of those using pantoprazole (p < 0.001). H. pylori infection was associated with an increased probability of erosive esophagitis healing. CONCLUSIONS: Pantoprazole once daily was superior to nizatidine b.i.d. in producing complete heartburn relief in a mixed population of GERD patients and in achieving erosion healing. The proportions of patients with complete symptom relief were greater with pantoprazole after 7 days of therapy than with nizatidine after 28 days. The present study data suggest that pantoprazole is a highly effective first-line therapy for the management of gastroesophageal reflux disease in a primary care practice setting.     

Influence of Helicobacter pylori eradication therapy on 13C aminopyrine breath test: comparison among omeprazole-, lansoprazole-, or pantoprazole-containing regimens

OBJECTIVE: Proton pump inhibitors and antimicrobial agents are widely used to eradicate Helicobacter pylori (H. pylori) infection. In the general population the prevalence of infection and of polypharmacy increases the possibility of drug-drug interactions during H. pylori eradication therapy. The purpose of the present study was to assess the prevalence, degree, and clinical relevance of metabolic interference with the cytochrome P450 enzymatic system occurring during 1 wk of administration of omeprazole, lansoprazole, or pantoprazole followed by the association of clarithromycin and metronidazole for another week. The 13C aminopyrine breath test (ABT) was chosen to screen for possible interactions. METHODS: We studied 30 patients referred to our Unit for H. pylori eradication therapy. They were randomized to receive either omeprazole (20 mg b.i.d.), lansoprazole (30 mg b.i.d.), or pantoprazole (40 mg b.i.d.) for 2 wk. During the second week clarithromycin (250 mg b.i.d.) and metronidazole (500 mg b.i.d.) were added. ABT was performed before, and at the end of the first and second week of therapy. Percentage of the administered dose of 13C recovered per hour at the peak (percent 13C dose/h at the peak) and cumulative percentage of administered dose of 13C recovered over time at 120 min (percent 13C dose cum120) were the ABT evaluated parameters. RESULTS: At baseline all patients showed a normal liver function. In individual patients during treatment we observed various liver metabolic interactions both as inhibition and induction, as well as after the first and the second week of therapy. However, mean modifications of the ABT parameters during the 2 weeks of therapy were not statistically significant compared to baseline values. None of the patients who had ABT variations complained of side effects. CONCLUSIONS: H. pylori eradication therapy interferes with cytochrome P450-dependent liver metabolic activity. However, the clinical relevance of these metabolic interactions is not yet apparent, and further investigation is needed. H. pylori eradication therapy appears safe, but these interactions should be considered in the choice of proton pump inhibitor and antimicrobial agents.     

Gastric and esophageal pH in patients with Barrett's esophagus treated with three esomeprazole dosages: a randomized, double-blind, crossover trial

BACKGROUND: It has been suggested that patients with Barrett's esophagus (BE) are unusually resistant to the antisecretory effects of proton pump inhibitors (PPIs). OBJECTIVES: To compare intragastric and intraesophageal acidity in patients with BE receiving esomeprazole 40 mg three times daily (t.i.d.), esomeprazole 40 mg twice daily (b.i.d.), and esomeprazole 20 mg t.i.d. METHODS: In this randomized, double-blind, three-way crossover study, patients with long-segment BE received each of the three esomeprazole dosages for 5 days separated by 10-14-day washout periods. Intragastric and intraesophageal pHs were measured for 24 h on day 5. RESULTS: Among 31 patients with evaluable pH data, intragastric pH was >4.0 for 88.4%, 81.4%, and 80.4% of day 5 after treatment with esomeprazole 40 mg t.i.d., 40 mg b.i.d., and 20 mg t.i.d., respectively. Esomeprazole 40 mg t.i.d. was significantly more effective than the other dosages (p < 0.01). Intraesophageal pH was <4.0 for mean values of <5% of the monitoring period with all the three dosing regimens, but esophageal pH remained <4.0 for >5% of the time in 16%, 23%, and 19% of patients receiving esomeprazole 40 mg t.i.d., 40 mg b.i.d., and 20 mg t.i.d., respectively. All dosages were well tolerated. CONCLUSIONS: All the three esomeprazole dosages significantly decreased intragastric acidity and reduced esophageal acid exposure to mean normal values in the total group of patients with BE. However, abnormal esophageal acid exposure continued in 16-23% of patients despite the significant decrease in gastric acidity. These results suggest that the apparent "PPI resistance" described in patients with BE may be caused by their profound reflux diathesis rather than by gastric resistance to the antisecretory effects of PPIs.     

Eradication rates of helicobacter pylori infection with second-line treatment: non-ulcer dyspepsia compared to peptic ulcer disease

BACKGROUND/AIMS: Initial proton pump inhibitor (PPI)-based triple therapy for Helicobacter pylori (H. pylori) infection is less effective in patients with nonulcer dyspepsia (NUD) than those with peptic ulcer disease (PUD). To date, there have been no studies on the difference in eradication rates in NUD compared to PUD with regard to second-line therapy. Therefore, we retrospectively analyzed the difference in eradication rates of a second-line quadruple therapy for NUD and PUD patients. METHODOLOGY: Between June 2003 and December 2005, patients who failed to respond to initial PPI-based triple therapy, received 7 days of quadruple therapy (PPI b.i.d., bismuth 300mg q.i.d., metronidazole 500mg t.i.d., tetracycline 500mg q.i.d.) as a second-line treatment regimen. Four weeks after the completion of the course of medication, a 13C-urea breath test was performed for detection of H. pylori. RESULTS: A total of 87 patients received second-line quadruple therapy. Of these, 43 patients had NUD and 44 patients had PUD (19 gastric ulcers, 23 duodenal ulcers, 2 both ulcers). The eradication rates were 76.7% (33/43) in the NUD group and 90.9% (40/44) in the PUD group by per-protocol analysis. Therefore, the eradication rates in the NUD group were significantly lower than those in the PUD group (p = 0.034). CONCLUSIONS: A 7-day bismuth-based second-line quadruple therapy for H. pylori infection was less effective in patients with NUD than those with PUD. Therefore, a more potent second-line treatment regimen or extension of treatment duration of quadruple therapy should be considered for the eradication of H. pylori in patients with NUD.     

Ranitidine Bismuth Citrate With Clarithromycin Given Twice Daily Effectively Eradicates Helicobacter pylori and Heals Duodenal Ulcers

Objective : Ranitidine bismuth citrate (RBC) b.i.d. with Clarithromycin q.i.d. eradicates Helicobacter pylori (H. pylori ) in 82–94% of patients, and heals duodenal ulcers in 88–90% of patients. This double blind, placebo-controlled study examines the efficacy of a simpler b.i.d. treatment regimen, and examines the potential benefit of including a second antibiotic, metronidazole, to the b.i.d. treatment regimen. Methods : A total of 648 patients with active duodenal ulcer received RBC 400 mg b.i.d. for 4 wk, coprescribed with Clarithromycin 250 mg q.i.d. , Clarithromycin 500 mg b.i.d. , or Clarithromycin 500 mg b.i.d. with metronidazole 400 mg b.i.d. for the first 2 wk of treatment. Endoscopies were performed prestudy, after 4 wk of treatment, and at least 4 wk posttreatment. H. pylori status was assessed by CLOtest, ¹³C-urea breath test (UBT), and histology prestudy, and by UBT and histology at least 4 wk posttreatment. Adverse events were recorded at each visit. Results : All three regimens were highly effective and well tolerated. H. pylori eradication rates were 84–94% and duodenal ulcer healing rates were 92–96% (observed data). Highest H. pylori eradication and ulcer healing rates were achieved with RBC 400 mg b.i.d. with Clarithromycin 500 mg b.i.d. Conclusion : Ranitidine bismuth citrate with Clarithromycin 500 mg b.i.d. provides an effective, simple and well tolerated regimen for the eradication of H. pylori and healing of duodenal ulcers.