Betsy L. Pilmer

Acid suppression in healthy subjects following lansoprazole or pantoprazole

To compare the effect of lansoprazole, 30 mg once daily, with that of pantoprazole, 40 mg once daily, for the inhibition of gastric acid secretion.

A comparison of simplified lansoprazole suspension administered nasogastrically and pantoprazole administered intravenously: effects on 24‐h intragastric pH

To compare the 24‐h intragastric pH effects of simplified lansoprazole suspension, 30 mg, administered nasogastrically, with pantoprazole, 40 mg, administered intravenously.

Evaluation of the pharmacokinetics and pharmacodynamics of intravenous lansoprazole

Aim : To compare the pharmacokinetics and pharmacodynamics of lansoprazole 30 mg administered intravenously in 0.9% NaCl or in polyethylene glycol, or orally.

Proton Pump Inhibitors: Effective First-Line Treatment for Management of Dyspepsia

The aim of this study was to evaluate the reasons for trial exclusion among dyspeptic patients and estimate the proportion that may have benefited from proton pump inhibitor (PPI) therapy. Stringent inclusion criteria for enrollment in two multicenter functional dyspepsia trials included dyspepsia (predominant persistent/recurrent upper abdominal discomfort [UAD] during the prior 3 months) of at least moderate intensity during ≥30% of days during the prior 2 to 3 weeks. Exclusion criteria were mild/infrequent UAD; heartburn and UAD of equal frequency; predominant heartburn with UAD; endoscopic evidence of erosive esophagitis or Barrett’s or gastric and/or duodenal erosions (>5) or ulcers; irritable bowel syndrome (IBS); other gastrointestinal diagnoses; or other “non-categorized” disorders. Of 2,588 screened patients, 1,667 were excluded. Excluded patients by category had mild/infrequent UAD (12.5%, n=324), heartburn and UAD of equal frequency (1.1%, n=29), predominant heartburn with UAD (11.6%, n=300), endoscopic evidence of erosive esophagitis or Barretts (6.2%, n=160), gastric and/or duodenal erosions (1.4%, n=36), gastric and/or duodenal ulcers (2.0%, n=53), IBS (7%, n=180), “other” gastrointestinal diagnoses (2.8%, n=73), or other “non-categorized” disorders (19.8%, n=512). Fifty-four percent of patients (902/1,667) had symptoms/diagnoses that would be expected to improve with PPI therapy. Individuals with IBS, “other,” or “non-categorized” disorders were considered to have symptoms unlikely to respond to PPI treatment. Empiric PPI treatment would be expected to provide symptom relief to the majority of dyspepsia sufferer who present in clinical practice. PPIs represent the best currently available therapy for acid-related disorders and should be considered the first-line management approach in patients with uninvestigated dyspepsia.

Intravenous and oral lansoprazole are equivalent in suppressing stimulated acid output in patient volunteers with erosive oesophagitis

Background : Some patients requiring acid suppression may be unable to take oral medications.

Bioavailability of lansoprazole granules administered in juice or soft food compared with the intact capsule formulation

BACKGROUND The ability to administer the contents of an encapsulated-dose formulation in liquids or soft foods without compromising drug bioavailability is highly desirable for patients who are unable to swallow or have difficulty swallowing. OBJECTIVE The purpose of this study was to compare the bioavailability of lansoprazole granules administered in 2 types of juice and a soft food with that of the intact capsule administered with water. METHODS Healthy adult volunteers were eligible for this single-center, Phase I, single-dose, randomized, open-label, 4-period crossover study. Subjects received the enteric-coated granular contents of a 30-mg lansoprazole capsule in 3 test regimens (in 180 mL of orange juice, 180 mL of tomato juice, or 1 tablespoon of strained pears, each followed by 180 mL of water) and 1 reference regimen (the 30-mg intact capsule with 180 mL of water). The regimens were rotated at > or = 6-day intervals so that each subject received all 4 regimens. Blood samples for pharmacokinetic analyses were obtained during the 12 hours after each regimen. RESULTS Twenty healthy adult volunteers (10 men, 10 women; mean age, 36 years [range, 19-53 years]) completed this study. Bioavailability of the 3 test regimens was assessed using the two 1-sided tests procedure for mean maximum plasma concentration and area under the plasma concentration-time curve (AUC) from time 0 through the last measurable concentration and AUC from time 0 to infinity. These results were compared with that of the intact capsule. This comparison indicated that the 90% CIs for all 3 test regimens were within the acceptable bioequivalence range of 0.80 to 1.25. Lansoprazole was well tolerated, with most of the adverse events being mild. Headache was the most frequently reported adverse event. CONCLUSION The results of this study indicate that the bioavailability of lansoprazole granules, when administered in orange juice, tomato juice, or a small amount of strained pears, was similar to that of the intact capsule in these healthy adult volunteers.

Comparison of the Effects of Single and Repeated Oral Doses of Lansoprazole and Rabeprazole on Ambulatory 24-Hour Intragastric pH in Healthy Volunteers

AbstractBackground: As the comparative pharmacokinetics and pharmacodynamics of lansoprazole and rabeprazole have not previously been studied, we set out in this study to compare the pharmacokinetics and pharmacodynamics of single and repeated daily doses of lansoprazole 15mg and 30mg with those of rabeprazole 10mg and 20mg. Methods: This was an open-label, randomised, crossover, two-centre study in 72 healthy volunteers. Each subject received each of the four treatments for 5 days, with 2-week washout periods. Continuous 24-hour intragastric pH and pharmacokinetics were studied on days 1 and 5. Results: Mean 24-hour pH and percentage time for pH >4 were not significantly different between lansoprazole 30mg and rabeprazole 20mg. Mean 24-hour pH and percentage time for pH >4 were significantly greater after lansoprazole 30mg and rabeprazole 20mg than after lansoprazole 15mg and rabeprazole 10mg, respectively. Lansoprazole resulted in greater acid suppression during hours 0–5 on days 1 and 5, whereas rabeprazole had greater suppression during hours 11–24 on day 5. Time to maximum plasma concentration was significantly shorter for lansoprazole on both days. Conclusion: Lansoprazole had a consistently faster onset of action, whereas rabeprazole had a greater effect during the evening hours after 5 days of administration.

1152 Distinguishing the Impact of Dexlansoprazole on Heartburn Versus Regurgitation in Patients With NERD or EE

Purpose: To determine the impact of dexlansoprazole MR (DEX) on heartburn (HB) and regurgitation severity in nonerosive gastroesphophageal reflux disease (NERD) and erosive esophagitis (EE) patients. Methods: This was a post hoc analysis of patients enrolled in phase 3 studies either assessing the efficacy and safety of DEX vs placebo (PLB) for 24-hour HB relief in NERD or DEX vs lansoprazole (LAN) in EE healing. DEX 30 mg, DEX 60 mg, and PLB were administered to 315, 315, and 317 endoscopically confirmed NERD patients, respectively, in a randomized, double-blind, 4-week study. NERD patients were to have a ≥6 month history of HB. In two 8-week, double-blind, randomized healing studies, 2737 endoscopically confirmed EE patients received DEX 60 mg or LAN 30 mg. In all studies, the Patient Assessment of Upper Gastrointestinal-Symptom Severity questionnaire (PAGISYM) was administered at baseline to assess symptom severity. The PAGI-SYM was also completed at Weeks 2 and 4 of the NERD study, and at Weeks 4 and 8 during the EE healing trials. The PAGI-SYM, a validated questionnaire, includes items assessing severity of HB and regurgitation on a scale of 0 to 5 (no symptoms, mild, moderate, severe and very severe symptoms) yielding a HB/regurgitation subscale. Using the PAGI-SYM questions included in this subscale, we defined separate subscales for HB and regurgitation. Among patients who had both symptoms at baseline (defined as at least mild HB and at least mild regurgitation in the individual subscales), we looked at the change from baseline (CFB) in individual HB and regurgitation subscales along with the original combined HB/regurgitation subscale. Negative CFBs indicate symptom improvement. A CFB of ≥0.55 was considered the minimally important difference for the HB/regurgitation subscale score. Results: In the NERD study, 661 patients had both HB and regurgitation at baseline, as did 1909 patients in the EE study. Table 1 and Table 2 provide the mean CFB in the subscale scores for the NERD and EE patients, respectively. NERD patients receiving DEX 30 and 60 mg experienced significantly greater improvements in symptom severity for both HB and regurgitation compared to PLB. EE patients receiving DEX 60 mg had significantly greater improvements in HB/regurgitation and HB-only subscales at Week 4 compared to those receiving LAN. Conclusions: DEX appears to be effective in improving both the mechanical (regurgitation) and chemical (HB) aspects of GERD symptoms and this improvement is maintained for the duration of treatment. Table 1. NERD