Suppression of gastric acid with intravenous esomeprazole and omeprazole: results of 3 studies in healthy subjects.

OBJECTIVE: To identify the optimal pharmacodynamic dosing regimen for esomeprazole administered intravenously (i.v.) and to compare acid suppression with various esomeprazole i.v. and omeprazole i.v. dosing regimens. METHODS: A total of 90 healthy Helicobacter pylori-negative subjects participated in three randomized, crossover studies of esomeprazole i.v. Comparative acid output study: an open-label study that compared single 40 mg i.v. doses (administered over 30 min) of esomeprazole and omeprazole. Dose-ranging study: an open-label study that compared acid control with five different doses of esomeprazole i.v., administered over 24 h. Comparative pH study: a double-blind study that compared esomeprazole i.v. and omeprazole at doses of 80 mg (over 30 min) + 8 mg/h (for 23.5 h). RESULTS: In the comparative acid output study, estimated mean pentagastrin-stimulated acid output was reduced from 33.9 mmol/h at baseline to 5.4 mmol/h at 4 - 5.5 h with esomeprazole vs. 9.5 mmol/h with omeprazole (p < 0.001). In the dose-ranging study, the 80 + 8 mg/h regimen provided a greater mean time with pH > 6 (12.6 h) than the lower doses (11.0 and 10.7 h for 40 + 8 mg/h and 80 + 4 mg/h, respectively) and significantly more time with pH > 4 (21.5 vs. 19.7 and 19.2 h, respectively; p < 0.05). In the comparative pH study, the mean number of h with pH > 4 was similar between esomeprazole (21.4 h) and omeprazole (21.1 h). CONCLUSIONS: Esomeprazole was superior to omeprazole in reducing stimulated acid secretion. Control of intragastric pH was similar for esomeprazole and omeprazole at a dose of 80 + 8 mg/h. An esomeprazole i.v. dosage regimen of 80 + 8 mg/h appeared to be optimal for acid suppression in healthy subjects under study.

Does esomeprazole prevent post-operative nausea and vomiting?

BACKGROUND: Esomeprazole is a potent proton pump inhibitor (PPI), reducing acid production as well as gastric juice volume. This study evaluated the possible beneficial effect of esomeprazole on reducing post-operative nausea and vomiting (PONV). METHODS: Patients undergoing laparoscopic or open gynaecological surgery, or laparoscopic cholecystectomy were randomized to receive three peri-operative doses double blindly of either esomeprazole 40 mg or placebo, given intravenously or orally. All patients were given a standardized anaesthesia regimen including fentanyl and sevoflurane/nitrous oxide. RESULTS: The study population consisted of 284 patients. Demographic data and known PONV risk factors were similar for the two treatment groups. PONV was observed in 77% of patients on esomeprazole vs. 81% on placebo (NS) and rescue antiemetic medication was needed in 56% vs. 53%, respectively (NS). The proportion of patients that vomited during 0-24 h was lower on esomeprazole than placebo (38% vs. 49%; NS), and the mean amount of vomit was significantly lower (52 vs. 86 g; P < 0.05). The use of neostigmine, use of opioids and type of surgery were significant risk factors for PONV (P < 0.05). The 24-h incidence of PONV was 63% after laparoscopic gynaecology, 80% after laparoscopic cholecystectomy and 88% after open gynaecological laparotomy, whereas laparoscopic cholecystectomy had the lowest risk when corrected for other risk factors of PONV. CONCLUSION: Esomeprazole had no clinically relevant effect on the overall 24-h incidence of PONV. However, esomeprazole significantly reduced the total amount of vomit during 24-h post-operatively. This may be of value in patients with an increased risk of pulmonary aspiration.

Induction and distribution of intestinal immune responses after administration of recombinant cholera toxin B subunit in the ileal pouches of colectomized patients.

The induction and dissemination of mucosal immune responses to recombinant cholera toxin B subunit (rCTB) administered into the ileal pouches of patients, who had been colectomized because of ulcerative colitis, was analyzed. Biopsies from the duodenum and ileal pouch were collected, along with peripheral blood and ileostomy fluids. Two immunizations induced strong CTB-specific immunoglobulin A (IgA) antibody-secreting cell (ASC) responses in the duodenum in five of five patients, whereas weaker and less-frequent ASC responses were noted in the ileal pouch. Intestine-derived CTB-specific IgA ASCs were found in peripheral blood in three of the five patients. The vaccination also induced significant IgA antitoxin titer rises in ileostomy fluid in all of the patients. Increased production of gamma interferon in cell cultures from the ileal pouch was found in four of five patients after the vaccination. These results clearly indicate that rCTB administered into the distal ileum is capable of inducing B-cell responses in the "entire" small intestine and that homing of immunocompetent cells occurs preferentially to the duodenum.

Immune responses in ileostomy fluid and serum after oral cholera vaccination of patients colectomized because of ulcerative colitis.

The capacity of an oral inactivated B-subunit-whole-cell cholera vaccine to induce immune responses in patients colectomized due to ulcerative colitis was studied. Two doses of vaccine induced significant mucosal immunoglobulin A (IgA) antibody responses in ileostomy fluid against cholera toxin in 14 of 15 (93%) patients and against whole vibrios in 9 of 15 (60%) cases. The serological responses were lower (but not significantly) than those observed in healthy Swedish volunteers. Increased IgA antitoxin levels were found in ileostomy fluid as late as 2 years after vaccination.

Kinetics of local and systemic immune responses to an oral cholera vaccine given alone or together with acetylcysteine.

The possibility that a mucolytic drug, i.e., acetylcysteine, given orally may enhance the gut mucosal or systemic immune response to an oral B-subunit-whole-cell (B-WC) cholera vaccine was evaluated for 40 adult Swedish volunteers, and the kinetics of the immune responses were monitored for responding volunteers. Two doses of vaccine induced similar frequencies of immunoglobulin A (IgA) and IgG antitoxin responses (80 to 90%) and vibriocidal titer increases (60 to 65%) in serum irrespective of whether the vaccine was given alone or together with 2 g of acetylcysteine. In feces the frequencies of IgA antitoxin (67%) and antibacterial (33 to 40%) antibody responses were also comparable in the two immunization groups. Six months after vaccination, IgA and IgG antitoxin as well as vibriocidal antibody titer increases in serum could still be detected in approximately 80% of initially responding vaccinees. Significantly elevated fecal antitoxin and antibacterial IgA antibody levels were found in, respectively, 50 and 43% of those volunteers who initially had responded to the vaccine. Determination of IgA antibodies in feces does not seem to offer any advantages compared to determination in serum for assessment of immune responses after immunization with inactivated cholera vaccine.