Median Intragastric pH Research Articles

Prediction of the Drug-Drug Interaction Potential between Tegoprazan and Amoxicillin/Clarithromycin Using the Physiologically Based Pharmacokinetic and Pharmacodynamic Model.

Tegoprazan is a novel potassium-competitive acid blocker. This study investigated the effect of drug-drug interaction on the pharmacokinetics and pharmacodynamics of tegoprazan co-administered with amoxicillin and clarithromycin, the first-line therapy for the eradication of Helicobacter pylori, using physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) modeling. The previously reported tegoprazan PBPK/PD model was modified and applied. The clarithromycin PBPK model was developed based on the model provided by the SimCYP® compound library. The amoxicillin model was constructed using the middle-out approach. All of the observed concentration-time profiles were covered well by the predicted profiles with the 5th and 95th percentiles. The mean ratios of predicted to observed PK parameters, including the area under the curve (AUC), maximum plasma drug concentration (Cmax), and clearance, were within the 30% intervals for the developed models. Two-fold ratios of predicted fold-changes of Cmax and AUC from time 0 to 24 h to observed data were satisfied. The predicted PD endpoints, including median intragastric pH and percentage holding rate at pH above 4 or 6 on day 1 and day 7, were close to the corresponding observed data. This investigation allows evaluation of the effects of CYP3A4 perpetrators on tegoprazan PK and PD changes, thus providing clinicians with the rationale for co-administration dosing adjustment.

The appropriate cutoff gastric pH value for Helicobacter pylori eradication with bismuth-based quadruple therapy.

This study aimed to investigate whether an increased proton pump inhibitor (PPI) dose enhanced the efficacy of Helicobacter pylori (H.pylori) eradication and determine the appropriate cutoff intragastric pH value that could predict H.pylori eradication with bismuth-based quadruple therapy. A total of 207 H.pylori infected, treatment naive patients were enrolled in this prospective, open-label, randomized controlled trial. Patients were randomly allocated into Eso40-group (esomeprazole 40mg bid) and Eso20-group (esomeprazole 20mg bid), and their CYP2C19 genotyping status was assessed. The 24-h intragastric pH monitoring on day 7 was performed, and percentage of time gastric pH≥3, ≥4, ≥5, and ≥6 (pH holding time ratios; HTRs) were measured. H.pylori eradication was evaluated using 13 C-urea breath test. No significant difference in the eradication rates was observed between two groups. The median 24-h intragastric pH value was not significant different between two groups but the Eso40 Group had a significant higher pH4 HTRs (91.11% [95%CI: 87.50%-95.83%] vs. 95.83% [95.83%-100%]; p=.002). Additionally, the median 24-h intragastric pH value showed significantly difference between two groups in EM genotype (Eso20 Group 6.00 [95%CI; 5.75-6.15] vs. Eso40 Group 6.30 [6.05-6.30]; p=.019). Similar results were observed in pH4 HTRs. There were significant differences in intragastric pH value (6.10 [95%CI: 4.40-7.00] vs. 5.65 [4.85-5.95], p=.038) and in pH4 HTRs (96% [95%CI: 92.00%-96.00%] vs. 87.5% [67.00%-100.0%], p=.019) between eradication-successful and eradication-failed patients. Statistical analysis suggested that the median intragastric pH=5.7 could identify the success of H.pylori eradication. Bismuth-based quadruple therapy resulted in high H.pylori eradication rates either in PPI standard or double doses. Double dose of esomeprazole is associated with better intragastric acid suppression. A median 24-h intragastric pH of 5.7 could be appropriate cutoff value for predicting the successful H.pylori eradication.

A randomized, crossover pharmacodynamic study of immediate-release omeprazole/sodium bicarbonate and delayed-release lansoprazole in healthy adult volunteers.

Proton pump inhibitors (PPIs) effectively block gastric acid secretion and are the treatment of choice for heartburn. PPIs differ, however, in onset of action and bioavailability. In this single‐center, open‐label, three‐way crossover study, onset of action of immediate‐release omeprazole 20 mg/sodium bicarbonate 1100 mg (IR‐OME) and delayed‐release (DR) lansoprazole 15 mg was evaluated in 63 healthy fasting adults. Subjects were randomized to once daily IR‐OME, or DR‐lansoprazole, or no treatment for 7 days. The primary efficacy endpoint was the earliest time where a statistically significant difference was observed between IR‐OME and DR‐lansoprazole in median intragastric pH scores for three consecutive 5‐min intervals on day 7. Secondary endpoints compared effects of active treatments on days 1 and 7 (e.g., time to sustained inhibition, percentage of time with pH >4). A significant difference in median intragastric pH favoring IR‐OME was observed on day 7 starting at the 10‐ to 15‐min interval postdosing (P = 0.024) and sustaining through the 115‐ to 120‐min interval (P = 0.017). On day 1, IR‐OME achieved sustained inhibition of intragastric acidity significantly faster than DR‐lansoprazole. IR‐OME maintained pH >4 significantly longer than DR‐lansoprazole over a 24‐h period (P = 0.007) on day 7. Overall, results of this study demonstrate IR‐OME is safe and well tolerated and that treatment with IR‐OME results in significantly faster onset of action and better gastric acid suppression at steady state than DR‐lansoprazole.

Gastro-esophageal reflux and antisecretory drugs use among patients with chronic autoimmune atrophic gastritis: a study with pH-impedance monitoring.

Patients with chronic autoimmune atrophic gastritis (CAAG) often refer digestive symptoms and are prescribed antisecretory medications. Aims were to investigate: (i) gastro-esophageal reflux (GER), (ii) psychopathological profile, (iii) frequency of use and clinical benefit of antisecretory drugs. Prospective observational study on 41 CAAG patients who underwent: 24 h multichannel intra-luminal impedance-pH (MII-pH) monitoring off-therapy, standardized medical interview and psychological questionnaire (i.e., SCL-90R). The medical interview was repeated at least 1 month after MII-pH in patients who were using antisecretory drugs. Statistical analysis was performed calculating median (10th-90th percentiles) and risk ratios (RR) with 95% confidence interval. Median intra-gastric pH was 6.2 (4.6-7.0). One patient had acid reflux (AC) associated with symptoms, five had increased total reflux number and four had symptoms associated to non-acid reflux (NA) (patients referred as 'GER positive'). Using patients 'GER negative' with normal SCL-90R as reference, the RR of being symptomatic in patients GER positive was 2.1 (1.1-4.1) if SCL-90R was normal and 0.9 (0.5-1.7) if it was altered (difference in RR significant being p = 0.04). Seventeen/28 (61%) symptomatic patients were on antisecretory drugs, which were stopped in 16 of them according to results of MII-pH and clinical evaluation after 574 days (48-796) showed that symptoms were unchanged. In patients with CAAG (i) AC reflux rarely occurred whereas increased NA reflux was not infrequent both being related to symptoms in some patients, (ii) psychopathological profile has a role in symptoms' occurrence, (iii) antisecretory drugs were generally inappropriately used and clinically ineffective.

Randomized, Placebo-Controlled, Crossover Pharmacodynamic Study Comparing the Effects of Zegerid® Capsule to Prevacid® Delayed-Release Capsule

Purpose: The primary objective was to evaluate the difference in the onset of action between two PPIs in fasting subjects on the seventh day of treatment. The secondary objectives included evaluations such as the difference in the onset of action in fasting subjects on the 1st day of treatment, the median time to an intragastric pH >4.0 for 10 consecutive minutes after drug administration on day 1 and day 7 of treatment, etc. Methods: Subjects were healthy male or female non-Asian adults within the age range of 18-65 years. Subjects were randomized to a three-way crossover to either Zegerid Capsules (20 mg omeprazole/1100 mg sodium bicarbonate), Prevacid Capsules (15 mg lansoprazole), or no-treatment. The treatment or no-treatment periods were 7 days. There was a minimum two-week washout period between treatments. Subjects underwent a 24-hour intragastric pH study on the first and seventh days of each period. A total of 63 subjects were randomized, and 59 completed per protocol. The primary efficacy endpoint was the earliest time for which a statistically significant difference between the median intragastric pH scores for three consecutive five-minute intervals at steady-state on day 7. Secondary efficacy endpoints included evaluation of primary efficacy endpoint on day one, determination of the time to sustained difference in inhibition of intragastric acidity between the two active study treatments on day 1 and day 7, etc. A total of 14 subjects experienced 21 treatment-emergent adverse events. Results: Zegerid achieved significant difference over Prevacid on day 7 for all of the five-minutes postdose intervals beginning at the 10-15 minute interval (p = 0.0242) and sustaining through the 115-120 minute interval (p = 0.0170). On day 7, over the 24-hour period, Zegerid maintained pH > 3.5 and 4 significantly longer than Prevacid (p=0.0075), and held the pH > 3.5 and 4 more than 50% of the time (at least 12 hours; p=0.0209). Zegerid maintained the pH >4 significantly longer than Prevacid during the first four hours after dosing, with the first dose on day 1 (p= 0.0021), and the last dose on day 7 (p <0.0001). Conclusion: Zegerid capsules provide a significantly stronger acid suppressing pharmacodynamic effect, both in onset and duration of effect, than Prevacid capsules. The results also confirmed significant pH control over placebo in both active treatments. Both Zegerid and Prevacid were safe and well-tolerated. Disclosure - Dr. McGraw, and O'Mullane are employees of Merck. Dr. Pratha is a Merck consultant, and was the investigator. Mr. Tobin is employed by the CRO that provided study support services for Merck (performed the analyses, etc.). This research was supported by an industry grant from Merck.

Comparison of the effect of a single dose of omeprazole or lansoprazole on intragastric pH in Japanese participants: A two-way crossover study

BackgroundIt is known that the pharmacokinetic profile of proton pump inhibitors (PPIs) after postprandial administration may differ among PPIs. The purpose of this study was to compare the inhibitory effects of gastric acid secretion by PPIs administered after a meal, based on a 24-hour intragastric pH monitoring. MethodsTen healthy men who provided written informed consent participated in the study. They were given a 20-mg omeprazole tablet and a 30-mg lansoprazole orally dispersing tablet in a two-way crossover manner. At baseline, the anti-HP-IgG antibody levels in blood and the pepsinogen (PG) I/II ratio were measured. Participants were given a standardized meal and 200 mL of water at 9:30 am, 13:30 pm, and 18.30 pm. Participants took the PPI after breakfast. ResultsTwo of the ten participants tested positive for Helicobacter pylori infection. The PG I/II ratio indicated negative gastric atrophy in all the participants. The percentage 24-hour intragastric pH > 4 holding times (median, range) with omeprazole and lansoprazole were 29.3, 19.3–50.0% and 27.8, 13.0–42.3%, respectively, which shows that with the administration of omeprazole, the pH was maintained at >4 for a longer period (p < 0.05). Each median intragastric pH value per hour at 3, 17, and 18 hours after a dose of omeprazole was significantly higher than that of lansoprazole (p < 0.05). ConclusionCompared with lansoprazole, a single postprandial dose of omeprazole showed a more rapid and sustained acid-inhibitory effect.

A comparison of the acid‐inhibitory effects of esomeprazole and rabeprazole in relation to pharmacokinetics and CYP2C19 polymorphism

Esomeprazole and rabeprazole are metabolised in the liver by means of the CYP2C19 enzyme, which has several functional genetic polymorphisms. Among Caucasians, 70% of the population has a fast metaboliser phenotype, 25-30% an intermediate and 2-5% a slow metaboliser phenotype. It is unknown whether different PPIs are affected to the same extent by these phenotypic differences. To compare the acid-inhibitory effects of esomeprazole 40 mg and rabeprazole 20 mg in relation to CYP2C19 genotype and pharmacokinetics. Eighteen healthy Helicobacter pylori-negative Caucasian subjects with CYP2C19*2-*6 and *17 genotype were included in a randomised investigator-blinded crossover study with esomeprazole 40 mg and rabeprazole 20 mg. Intragastric 24-h pH-monitoring was performed on days 0, 1 and 5 of oral dosing. Onset of acid inhibition during the first 4 h after administration did not differ significantly between PPIs. During the upright period, the proportion of time with pH >4 was significantly higher with esomeprazole compared to rabeprazole (52.2 vs. 40.3%, P = 0.003). At day 1 and 5, acid inhibition was significantly greater with esomeprazole than with rabeprazole (median intragastric pH: day 1: 3.7 vs. 3.0, P = 0.008; day 5: 4.7 vs. 3.8, P < 0.001; percentage of time pH >4: day 1: 45 vs. 39%, P = 0.054; day 5: 65 vs. 48%, P < 0.001). Differences in acid inhibition between wt/wt and wt/*2 genotype were significant for both PPIs. Once-daily dosing with esomeprazole 40 mg provides a more effective and faster acid-inhibitory effect than rabeprazole 20 mg. The acid-inhibitory effect of esomeprazole and rabeprazole are both influenced by CYP2C19 polymorphism.

Effect of Intravenous Esomeprazole 40 mg and Pantoprazole 40 mg on Intragastric pH in Healthy Subjects

<i>Objective</i>: The aim of this study was to compare the effect on intragastric acidity over 24 h on days 1 and 3 following treatment with intravenous (i.v.) esomepra-zole 40 mg (CAS for esomeprazole sodium: 161796-78-7) and pantoprazole 40 mg (CAS for pantoprazole sodium: 138786-67-1). <i>Methods</i>: In an open, randomised, two-way cross-over study, 36 healthy volunteers received esomeprazole (Nexium^®) 40 mg or pantoprazole 40 mg, both administered once daily as an i.v. bolus injection for 3 consecutive days. Continuous 24-h pH recordings were made under standardised conditions at baseline and on days 1 and 3 of each treatment period. The primary variable was the percentage of time with intragastric pH > 4 during a 24-h period. <i>Results</i>: Time with intragastric pH > 4 was significantly greater with esomeprazole than with pantoprazole during the first 4 h (47.8 % vs. 18.9 %), as well as for the 24-h period of day 1 and day 3 (day 1: 38.8 % vs. 23.7 %; day 3: 55.0 % vs. 35.2 %, p<0.0001 for all times examined). Mean of median intragastric pH with esome-prazole was significantly higher than with pantoprazole during the 24-h period (day 1: 3.2 vs. 2.2, p<0.0001; day 3: 4.3 vs. 3.1, p<0.00001). <i>Conclusion</i>: Esomeprazole administered as a 40 mg i.v. bolus injection provided faster and more effective control of intra-gastric acidity than a 40 mg i.v. bolus injection of pantoprazole, and also maintained pH > 4 longer both during the first 4 h on day 1 and during the 24-h period of day 1 and day 3 of dosing.

Direct Measurement of Gastroesophageal Reflux Episodes in Patients With Squamous Cell Carcinoma by 24-h pH-Impedance Monitoring

Recent studies have consistently reported a significant association between gastric atrophy and esophageal squamous cell carcinomas (ESCCs). However, causative factors responsible for the linkage remain to be clarified. Multichannel intraluminal impedance monitoring in conjunction with a pH sensor (MII-pH) is a reliable technique to evaluate gastroesophageal reflux (GER) episodes, independent of the acidity. We investigated the potential roles of GER in the pathogenesis of ESCC with MII-pH. From August 2008 to May 2010, 14 consecutive inpatients with superficial ESCCs (ESCC group) and 14 age- and sex-matched inpatients without any esophageal dysplastic lesions (non-ESCC group) were enrolled. Twenty-four hour portable MII-pH monitoring was performed under standard hospitalized conditions. The data of MII-pH were used to identify acid reflux (AR: pH drop below 4.0 during a reflux episode) and non-AR (NAR: pH drop above 4.0 during a reflux episode). The median intragastric pH of the ESCC group was 4.7 (2.3-6.4), implying hypochlorhydria in this patient group. The numbers of total reflux and NAR episodes in the ESCC group were significantly higher than those in the non-ESCC group (56 (43-87) vs. 35.5 (18-47), P=0.016 for total reflux and 46.5 (32-84) vs. 24.5 (8-37), P=0.012 for NAR), whereas the numbers of AR were similar in both groups. In addition, there was significance in the category of percentage time of bolus reflux episodes. Using MII-pH monitoring, we revealed the clinical significance of GER, especially NAR, in ESCCs. NAR may be a key factor in the link between gastric atrophy and ESCCs.

Characteristics of non-erosive gastroesophageal reflux disease refractory to proton pump inhibitor therapy

To investigate whether potent acid inhibition is effective in non-erosive reflux disease (NERD) refractory to standard rabeprazole (RPZ) treatment. We treated 10 Japanese patients with NERD resistant to standard dosages of RPZ: 10 mg or 20 mg od, 20 mg bid, or 10 mg qid for 14 d. All patients completed a frequency scale for symptoms of gastroesophageal reflux disease questionnaire frequency scale for the symptoms of GERD (FSSG); and underwent 24 h pH monitoring on day 14. With increased dosages and frequency of administration of RPZ, median intragastric pH significantly increased, and FSSG scores significantly decreased. With RPZ 10 mg qid, potent acid inhibition was attained throughout 24 h. However, five subjects were refractory to RPZ 10 mg qid, although the median intragastric pH in these subjects (6.6, range: 6.2-7.1) was similar to that in the remaining five responsive subjects (6.5, range: 5.3-7.3). With baseline RPZ 10 mg od, FSSG scores in responsive patients improved by > 30%, whereas there was no significant decrease in the resistant group. NERD patients whose FSSG score fails to decrease by > 30% after treatment with RPZ 10 mg od for 14 d are refractory to higher dosage.

Intragastric acidity during administration of generic omeprazole or esomeprazole - a randomised, two-way crossover study including CYP2C19 genotyping

Generic omeprazole has been approved in many countries for the treatment of acid-related gastrointestinal disorders. However, clinical studies comparing generic to original proton pump inhibitors are limited. To compare the effect of generic omeprazole 20 mg/day with esomeprazole 20 mg/day on intragastric acidity and to investigate the influence of the CYP2C19 metabolizer status. In this randomised, single-blinded, two-way crossover study, 24 healthy Helicobacter pylori-negative subjects, received generic omeprazole (Omep; Hexal AG, Holzkirchen, Germany) 20 mg once daily or esomeprazole 20 mg once daily for five consecutive days. Twenty-four-hour intragastric pH was recorded on day 5 of each treatment. CYP2C19 status was determined by polymerase chain reaction-restriction fragment length polymorphism. Over all, there were no statistically significant differences between generic omeprazole and esomeprazole with respect to median intragastric pH (3.5 and 3.9, P = 0.07), the total hours with intragastric pH >4 (10.4 and 11.3, P = 0.29), and during upright (9.6 and 9.1, P = 0.77) or supine (2.2 and 2.2, P = 0.94) position. However, in CYP2C19 rapid metabolizers, esomeprazole was superior to omeprazole, with the percentage of time with intragastric pH >3.0 and pH >3.5 being higher with esomeprazole than with generic omeprazole [Δ = 9% (P = 0.026) and Δ = 8% (P = 0.046), respectively]. Overall, generic omeprazole 20 mg appears to provide a similar intragastric acid control when compared with esomeprazole 20 mg. However, esomeprazole might be advantageous in subjects with a rapid CYP2C19 metabolizer status.

Relationship between the Acid-Inhibitory Effects of Two Proton Pump Inhibitors and CYP2C19 Genotype in Japanese Subjects: A Randomized Two-Way Crossover Study

This two-way crossover study investigated possible differences between the proton pump inhibitors, omeprazole and rabeprazole, in their effect on gastric acid secretion in Japanese subjects with differing cytochrome P450, family 2, subfamily C, polypeptide 19 (CYP2C19) genotypes. A total of 23 Helicobacter pylori-negative healthy volunteers received omeprazole 20 mg/day and rabeprazole 10 mg/day. Each drug treatment was given for a continuous 7-day period allocated in random order, with an interval of at least 1 week between drug treatment periods to allow for wash-out. Intragastric pH was measured on days 1 and 7. Overall median intragastric pH levels at 7 and 8 h after the first administration were significantly higher with omeprazole. There was no significant difference in intragastric pH in homozygous extensive metabolizers, whereas intragastric pH was significantly higher with omeprazole in combined data from heterozygous extensive metabolizers and poor metabolizers at 6, 7 and 8 h after the first drug administration. There were no significant differences in intragastric pH between omeprazole and rabeprazole irrespective of genotype on day 7 of administration. In conclusion, on day 1 the time to onset of the antisecretory action of 20 mg/day omeprazole was more rapid than that of 10 mg/day rabeprazole in Japanese individuals who have a higher incidence of the CYP2C19 poor metabolizer genotype, however by day 7 no difference in antisecretory effect was found, regardless of genotype.

Comparison Between Oral vs. Intravenous Administration of PPI with Gastric pH

Purpose: In patients with peptic ulcer bleeding, a proton pump inhibitor (PPI) is administered intravenously (IV) following endoscopic treatment. However, if oral administration (PO) of the PPI obtains the same antisecretory effect as IV administration of the PPI (IV PPI), PO PPI treatment will be more advantageous in shortening the length of a patient's hospital stay compared to IV PPI administration. Methods: The subjects of the current study included 51 patients with peptic ulcer bleeding who did not undergo endoscopic therapy and in whom a visible vessel or blood clot was present. These patients were randomized into two groups, one group receiving IV administration of the PPI (IV PPI group (n=26)) and a group in which the PPI was administered orally (PO PPI group (n=25)). The 24-hour intragastric pH was measured andthe hemostasis rate was compared between the two groups. Results: The hemostasis rate was 92.3% (24/26) in the IV PPI group and 92.0% (23/25) in the PO PPI group (p=0.936). The median 24-hour gastric pH value was 5.93±1.92 in the IV PPI group and 5.73±1.74 in the PO PPI group (p=0.748). Daytime median intragastric pH was 5.94±2.00 in the IV PPI group and 5.58±1.69 in the PO PPI group (p=0.861). Night-time median pH was 5.91±1.95 in the IV PPI group and 5.68±1.86 in the PO PPI group (p=0.624). The mean percent of cases in which gastric pH exceeded 6 was 62.3% in the IV PPI group and 58.5% in the PO PPI group (p=0.672). The difference in the cumulative frequency of cases did not reach a statistical significance. Conclusion: In patients with bleeding peptic ulcer, in which a visible vessel or blood clot was present, there were no significant differences in the intragastric pH and hemostasis rate between intravenous infusion of a PPI and the oral administration of a PPI.

Control of 24-hour Intragastric Acidity With Morning Dosing of Immediate-release and Delayed-release Proton Pump Inhibitors in Patients With GERD

To compare the effects of immediate-release omeprazole and 2 different delayed-release proton pump inhibitors on 24-hour intragastric acidity in gastroesophageal reflux disease patients. Because of its unique pharmacokinetic properties, immediate-release omeprazole does not need to be dosed before a meal to control intragastric acidity. Previous studies showed effectiveness of immediate-release omeprazole in controlling nocturnal intragastric acidity with bedtime dosing. This is the first study to compare the effects of prebreakfast dosing of immediate-release omeprazole and delayed-release lansoprazole and pantoprazole on 24-hour intragastric acidity. To compare the effects of prebreakfast dosing of immediate-release omeprazole 40 mg capsules, lansoprazole 30 mg capsules, and pantoprazole 40 mg tablets on 24-hour intragastric acidity. Fifty-five patients with gastroesophageal reflux disease received 7 consecutive once-daily morning doses of each drug in this open-label, randomized, 3-period crossover study. On day 7, intragastric pH was recorded for 24 hours. After 7 days, the percentage of time with intragastric pH >4 over 24 hours was 59.7% (14.3 hours) with immediate-release omeprazole, 48.8% (11.7 hours) with lansoprazole (P=0.005), and 41.8% (10.0 hours) with pantoprazole (P<0.001). Median intragastric pH was significantly higher with immediate-release omeprazole than with lansoprazole (P=0.003) or pantoprazole (P<0.001). All drugs were well tolerated. When dosed in the morning, immediate-release omeprazole provided significantly better control of 24-hour intragastric acidity than lansoprazole and pantoprazole.

Comparing the Acid-Suppressive Effects of Three Brands of Generic Lansoprazole with the Original: Pharmacokinetic Bioequivalence Tests Do Not Necessarily Guarantee Pharmacodynamic Equivalence

Generic drugs contain the same active ingredient as an original drug and have their bioequivalence proved by pharmacokinetic tests. However, few studies have been reported on whether these bioequivalence studies infer pharmacodynamic equivalence. In this study, in eight healthy Helicobacter pylori-negative CYP2C19 extensive metabolizers, we compared the acid-suppressive effects of repeated administration of 15 mg of three brands of generic lansoprazole, Taiproton, Tapizol, and Lansoral, with those of the original lansoprazole, Takepron. Median intragastric pH value for 24-h and % pH > 4 for daytime (08:00-20:00 h) and night-time were significantly higher with any lansoprazole formulation, compared with the control (P < 0.05, Wilcoxon signed-rank test). However, during the daytime, % pH > 4 with Tapizol was significantly lower than the original (P < 0.05). Compared with the original, no significantly larger, but no small range of inter-subject variations were observed in these two parameters for each of the three brands of generic lansoprazole (Bartlett test). Pharmacokinetic bioequivalence tests do not necessarily guarantee pharmacodynamic equivalence.

The effect of omeprazole paste on intragastric pH in clinically ill neonatal foals

Administration of omeprazole paste per os to healthy neonatal foals has been shown to effectively increase intragastric pH, but has not been evaluated in sick neonatal foals. To determine the effect of orally administered omeprazole paste on intragastric pH in clinically ill neonatal foals requiring nasogastric intubation. Intragastric pH was measured continuously for 24 h using an indwelling electrode and continuous data recording system in hospitalised neonatal foals age < or =2 days. Intragastric pH was measured for 12 h prior to (pretreatment period) and 12 h following (post treatment period) treatment with omeprazole paste (4 mg/kg bwt per os). All foals displayed periods of acidity (pH <4) prior to treatment. Statistical analysis compared pre- and post treatment mean and median intragastric pH, and percentage of time below pH 4. Eight foals were evaluated age 1-3 days, a gestational age of at least 320 days or reported to be full term. The mean (3.19 +/- 1.50 vs. 6.20 +/- 0.93) and median (4.6 +/- 1.7 vs. 6.86 +/- 0.89) pH were significantly higher and the percentage of time below pH 4 (32.25 vs. 1.1%) was significantly lower in the post treatment compared to the pretreatment period. Omeprazole paste effectively increases intragastric pH in clinically ill neonatal foals after one dose at 4 mg/kg bwt orally.

Stronger inhibition of gastric acid secretion by lafutidine, a novel H2 receptor antagonist, than by the proton pump inhibitor lansoprazole

To compare the antisecretory activity and plasma drug concentrations of a single oral dose of 10 mg lafutidine, a novel H2 receptor antagonist, with those of the proton pump inhibitor lansoprazole (LPZ) 30 mg. Ten volunteers without H pylori infection participated in this crossover study comparing lafutidine 10 mg with LPZ 30 mg. Intragastric pH was monitored for 6 h in all participants, and blood samples were collected from four randomly selected individuals after single-dose administration of each drug. The median intragastric pH was significantly higher in individuals who received lafutidine 10 mg than in those who received LPZ 30 mg 2, 3, 4, 5, and 6 h after administration. Maximal plasma drug concentration was reached more promptly with lafutidine 10 mg than with LPZ 30 mg. In H pylori-negative individuals, gastric acid secretion is more markedly inhibited by lafutidine than by LPZ.

Low‐dose intravenous pantoprazole for optimal inhibition of gastric acid in Korean patients

Proton-pump inhibitor (PPI) therapy for bleeding ulcers is more efficacious in Asian patients than in non-Asian patients. The aim of this study was to evaluate the efficacy of various doses of pantoprazole on intragastric acidity in Korean patients. A prospective randomized study was conducted in 52 patients either with bleeding peptic ulcers after successful endotherapy or who received endoscopic mucosal resection for gastric neoplasms. Patients were randomized into two doses of intravenous pantoprazole: 40 mg q.d. and 40 mg b.i.d. We compared these results with our preliminary study utilizing high-dose pantoprazole (80 mg + 8 mg/h). The potential contribution of CYP2C19 genetic polymorphisms and the presence of Helicobacter pylori were also assessed. Pantoprazole 40 mg b.i.d. and high-dose pantoprazole demonstrated better inhibition of intragastric acid than pantoprazole q.d. (P < 0.05). The pantoprazole 40 mg q.d. group exhibited significant variations in acid inhibition correlating with CYP2C19 genotype. Median 24 h pH values did not differ significantly between the pantoprazole b.i.d. and high-dose pantoprazole groups, regardless of H. pylori infection status. A median intragastric pH < 6.0 was observed in only three of 28 patients in the 40 mg b.i.d. group; these three patients were extensive metabolizers. A 40 mg b.i.d. dose of pantoprazole is sufficient to maintain pH > 6.0 in Korean patients, except for patients with extensive metabolizing CYP2C19 genotypes.

Acid-Suppressive Effects of Various Regimens of Omeprazole in Helicobacter pylori-Negative CYP2C19 Homozygous Extensive Metabolizers: Which Regimen Has the Strongest Effect?

To achieve more potent and long-lasting acid suppression, omeprazole was administered for 7 days in 5 regimens: 10, 20, and 40 mg once daily (od), and 10 and 20 mg twice daily (bid), in 7 healthy Helicobacter pylori-negative CYP2C19 homozygous extensive metabolizers, and intragastric pH was continuously measured. The median intragastric pH and percent time pH > 4.0 for 24 hours increased dose dependently with 10, 20, and 40 mg od. Ten and 20 mg bid wre comparable to 20 and 40 mg od, respectively. Concerning percent time pH > 4.0 in the nighttime (20:00-8:00 hours), 20 mg bid was significantly superior to 40 mg od (P < .05). In 4 of the 5 regimens, all 7 subjects had nocturnal acid breakthrough, whereas with 20 mg bid it occurred in only 3. We concluded that, considering nighttime acid suppression, omeprazole 20 mg bid had the strongest effect.

Pharmacokinetics and Pharmacodynamics of Lansoprazole in Children 13 to 24 Months Old With Gastroesophageal Reflux Disease

To evaluate the pharmacokinetics and pharmacodynamics of lansoprazole in children between 13 and 24 months of age with gastroesophageal reflux disease (GERD). From the population of 66 children with symptomatic GERD, erosive esophagitis (> or = grade 2) or esophageal pH < 4 for > 4.2% of the 24-h period who participated in a phase I/II, open-label, multicenter (11 sites) US study, a subanalysis of 8 toddlers between 13 and 24 months of age was performed. All children were treated, based on body weight, with lansoprazole 15 mg once daily for 8 to 12 weeks. If a child were still symptomatic after 2 weeks of treatment, then the dose of lansoprazole could be increased to twice daily at the discretion of the investigator. Pharmacokinetic parameters were assessed at day 5. Twenty-four-hour median intragastric pH and the percentage of time intragastric pH > 3 or > 4 were assessed at baseline and at day 5 of treatment. Symptom response was assessed by investigator interview and daily diary. Safety was monitored by physical examinations including vital signs, adverse event assessments and laboratory evaluations. Pharmacokinetic analysis of 5 children found a mean time to reach maximum concentration of 1.4 h, maximal plasma concentrations of 894 ng/mL, area under the concentration time curve of 1906 ng * h/mL and a half-life of 0.66 h. Significant (P < or = 0.027) increases from baseline to day 5 were observed in mean 24-h intragastric pH (2.76-3.52) and the percentages of time pH were > 3 (29.46%-55.36%) and pH was > 4 (16.96%-40.77%). Six of the 8 children had improvement in their overall GERD symptom severity on the basis of investigator assessment, and a reduction was seen in the percentage of days with moderate, severe or very severe GERD symptoms compared with baseline. The dosage of lansoprazole was increased in 3 of the 8 children. Median fasting serum gastrin level increased from 65.0 pg/mL at baseline to 136.5 pg/mL at the final visit. Treatment-related events were mild constipation (1 subject) and mild diarrhea (1 subject). Although larger studies are needed to confirm these results, lansoprazole displays pharmacokinetic and pharmacodynamic parameters in children between 13 and 24 months of age that are similar to those results observed in older children as well as adults.