omeprazole, Prilosec
Study of the electrospray ionization mass spectrometry of the proton pump inhibiting drug Omeprazole.

Weidolf L, Castagnoli N Jr.

AstraZeneca R&D, S-431 83 Molndal, Sweden. lars.weidolf astrazeneca.com

A detailed analysis of the product ion spectrum generated from the protonated molecule under ESI-MS/MS conditions using a triple quadrupole mass spectrometer is reported for the gastrointestinal proton pump inhibitor Omeprazole. Unambiguous molecular composition data of the fragment ions were obtained with the aid of regioselectively 14C-, 34S- and 18O-labeled analogs. Attempts have been made to provide rational pathways for the formation of the fragment ions from four protonated omeprazole species. These results will facilitate the characterization of the complex metabolic fate of Omeprazole in humans, which involves the excretion of at least 50 metabolites. Copyright 2001 John Wiley & Sons, Ltd.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11223960&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Protective effect of famotidine, omeprazole, and melatonin against acetylsalicylic acid-induced gastric damage in rats.

Sener-Muratoglu G, Paskaloglu K, Arbak S, Hurdag C, Ayanoglu-Dulger G.

Marmara University School of Pharmacy, Department of Pharmacology, Haydarpasa, Istanbul, Turkey.

It has been reported that both omeprazole and famotidine have a protective effect against gastric mucosal damage induced by acetylsalicylic acid (ASA) and other nonsteroidal anti-inflammatory drugs. Since active oxygen species and lipid peroxidation were reported to play a role in the pathogenesis induced by ASA, we aimed to study if omeprazole and famotidine have any antioxidant effect by comparing their protective effect with that of melatonin, an effective antioxidant and free radical scavenger. Mucosal damage was evaluated by macroscopic examination, histological analysis and by measurement of lipid peroxidation (LPO), glutathione (GSH), and myeloperoxidase (MPO) activity. Omeprazole (20 micromol/kg per os), famotidine (3 mg/kg per os), and melatonin (10 mg/kg intraperitoneally) significantly prevented gastric ulcerogenesis induced by ASA (200 mg/kg per os) and decreased the ulcer index. Gastric LPO and MPO activity that were increased significantly by ASA were decreased after treatment with omeprazole, famotidine, and melatonin. ASA treatment decreased significantly the gastric GSH levels, and pretreatment with omeprazole, famotidine, or melatonin increased it significantly. Famotidine and omeprazole decreased the gastric acidity, which was increased by ASA, whereas melatonin had no effect on this parameter. These findings suggest that active oxygene species and LPO have an important role in the pathogenesis of gastric mucosal damage induced by ASA and that both famotidine and omeprazole may be protective against this damage, although they were not as efficient as melatonin as an antioxidant. On the other hand, the antisecretory effect of omeprazole and famotidine may also be contributing to their antiulcer effect.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11281181&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Haloperidol-stomach lesions attenuation by pentadecapeptide BPC 157, omeprazole, bromocriptine, but not atropine, lansoprazole, pantoprazole, ranitidine, cimetidine and misoprostol in mice.

Bilic I, Zoricic I, Anic T, Separovic J, Stancic-Rokotov D, Mikus D, Buljat G, Ivankovic D, Aralica G, Prkacin I, Perovic D, Mise S, Rotkvic I, Petek M, Rucman R, Seiwerth S, Sikiric P.

Medical Faculty University of Zagreb, Croatia.

The focus was on haloperidol (central dopamine antagonist)-stomach lesion, a longly described suitable counterpart of dopamine blocker cysteamine-duodenal lesion. In this, the contribution of blockade of central/peripheral dopamine receptors and prostaglandins synthesis, along with influence of antiulcer agents was evaluated in mice. Male NMRI Hannnover mice were sacrificed 24 h after haloperidol (25 mg/kg b.w. i.p., given alone or with saline (haloperidol+saline) (i) or in combination (ii,iii)). Supporting central dopamine predominance for haloperidol stomach lesion induction, co-administration of peripheral dopamine receptor antagonist domperidone (5 mg/kg i.p.) (haloperidol+ domperidone) (ii), or prostaglandin synthesis inhibitor indomethacin (10 mg/kg s.c.) (haloperidol+ indomethacin) (iii) did not aggravate this lesion. (i) In haloperidol+saline challenged mice the lesions were inhibited by co-administration (/kg i.p.) of a gastric pentadecapeptide BPC 157, GlyGluProProProGlyLysProAlaAspAspAlaGlyLeuVal, M.W. 1419 (10 microg, 10 ng, 10 pg, but not 1 pg, 100 fg, 10 fg), bromocriptine (10 mg), omeprazole (10 mg, 100 mg, but not 1 mg). Atropine (10, 100, 200 mg), pirenzepine (10, 100, 200 mg), misoprostol (10, 100, 200 microg), pantoprazole (1, 10, 100 mg), lansoprazole (0.1, 1, 10 mg), cimetidine (10, 100, 200 mg) and ranitidine (10, 100, 200 mg) were not effective. (ii) Dopamine peripheral blockade influence: in haloperidol+domperidone mice, previously effective bromocriptine, pentadecapeptide BPC 157 (10 microg) or omeprazole (10 mg) did not attenuate stomach lesions. (iii) Prostaglandins synthesis blockade effect: in haloperidol+indomethacin mice, previously effective agents, bromocriptine or omeprazole were not active, while BPC 157 effect was only lessened.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11292068&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
[Cross reactivity among proton pump inhibitors: does it exits?]

[Article in Spanish]

Garmendia Zallo M, Sanchez Azkarate A, Kraemer Mbula R, Liarte Ruano I, Nunez Hernandez A, Cid De Rivera C.

Servicio de Alergologia, Hospital de Cruces, Barakaldo, Bizkaia, Spain.

BACKGROUND: There has been little research into adverse reactions to proton pump inhibitors (omeprazole and its analogs) of suspected allergic etiology. We found nine studies in the medical literature and only two of these describe cross reactivity between proton pump inhibitors detected by skin prick tests. CASE REPORT: We present a 24-year-old woman who twice developed total body pruritus and urticaria with facial angioedema 1-2 hours after ingesting an omeprazole capsule. In the second episode the patient also reported the sensation of having a lump in her throat. METHODS: Skin prick and intradermal tests were performed with omeprazole, pantoprazole, and lansoprazole, which were positive for the three proton pump inhibitors. For ethical reasons, oral challenge testing was not performed. CONCLUSION: The clinical picture and the positive skin test results suggest an IgE-mediated mechanism. Skin prick tests may be useful for the diagnosis of cases of suspected allergy to omeprazole and its analogs. We found cross reactivity between three proton pump inhibitors detected by skin tests.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15087098&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Effects of IY-81149, a newly developed proton pump inhibitor, on gastric acid secretion in vitro and in vivo.

Kwon D, Chae JB, Park CW, Kim YS, Lee SM, Kim EJ, Huh IH, Kim DY, Cho KD.

Department of Pharmacology and Toxicology, Il Yang Central Research Institute, Kyunggi-Do, Korea.

The inhibitory effects of IY-81149 (2-[[(4-methoxy-3-methyl)-2- pyridinyl]methyl-sulfinyl]-5-(1H-pyrol-1-yl)-1H-benzimidazole, CAS 172152-36-2), a newly developed proton pump inhibitor (PPI) on gastric acid secretion were investigated in vitro and in vivo. In rabbit parietal cell preparation, IY-81149 irreversibly inhibited H+/K(+)-ATPase in dose-dependent manner with an IC50 of pump inhibitory activity of 6.0 x 10(-6) mol/l and that of omeprazole (CAS 73590-58-6) was 1 x 10(-4) mol/l at pH 7.4. On cumulation of 14C-aminopyrine in histamine stimulated parietal cells, the IC50 of IY-81149 was 9.0 x 10(-9) mol/l and that of omeprazole was 1.9 x 10(-8) mol/l. The inhibition rates of IY-81149 and omeprazole at a concentration of 1 x 10(-9) mol/l in human parietal cells were 137% and 64%, respectively. In pylorus-ligated rats, IY-81149 showed a 2-3 times stronger inhibitory activity than omeprazole against gastric acid secretion. The ED50 of IY-81149 and omeprazole administered intraduodenally was 1.6 mg/kg and 3.8 mg/kg. In the case of oral administration, the ED50 of IY-81149 and omeprazole was 1.94 mg/kg and 5.64 mg/kg, respectively. But after 24 h administration, the anti-secretory activity of IY-81149 was lower than that of omeprazole at all doses tested. In anesthetized rats, IY-81149 dose-dependently increased gastric pH which was lowered by histamine infusion. In the case of i.v. injection, the ED50 of IY-81149 and omeprazole was 1.2 and 1.4 mg/kg and in the case of i.d. administration, the ED50 of IY-81149 and omeprazole was 3.9 and 4.1 mg/kg, respectively. IY-81149 also significantly inhibited pentagastrin-stimulated gastric secretion. Its ED50 was 2.1 mg/kg and that of omeprazole was 3.5 mg/kg with i.d. administration. In the case of i.v. injection, IY-81149 was equipotent to omeprazole. IY-81149 also inhibited gastric acid secretion strongly in fistular rats. The ED50 of IY-81149 administered intraduodenally was 0.43 mg/kg and that of omeprazole was 0.68 mg/kg. In Heidenhain pouch dogs, the acid output was completely blocked at 0.3 mg/kg, 135 min after i.v. administration. Omeprazole showed a similar effect as IY-81149. The histamine induced increase of acid output in the Heidenhain pouch dog was blocked by 71% 150 min after oral administration of enteric-coated IY-81149 at a dose of 3 mg/kg, and omeprazole showed similar effects. In conclusion, IY-81149 revealed the characteristics as a strong proton pump inhibitor, and its potency against gastric acid secretion was superior to that of the reference drug, omeprazole.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11304936&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Use of omeprazole during pregnancy--no hazard demonstrated in 955 infants exposed during pregnancy.

Kallen BA.

Tornblad Institute, University of Lund, Biskopsgatan 7, S-223 63, Lund, Sweden. embryol embryol.lu.se

OBJECTIVES: To evaluate the magnitude of possible fetal risks involved in maternal use of omeprazole during pregnancy. STUDY DESIGN: Infants whose mothers used omeprazole during pregnancy were identified from the Swedish Medical Birth Registry. A total of 955 exposed infants born in 1995-1999 were identified: 863 of which were exposed in early pregnancy and 131 later in pregnancy and 39 who had been exposed both in early and late pregnancy. Delivery outcome was studied: presence of congenital malformations, perinatal survival, low birth weight, low Apgar score and hospitalization up to the end of 1997. RESULTS: No clear-cut indication of ill effects were seen. Five infants were stillborn and the rate of congenital heart defects was slightly increased, but both effects may be random. CONCLUSIONS: The present dataset and previously published data give no reason for concern after exposure for omeprazole during pregnancy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11311763&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Stability of gastric secretory inhibition during 6-month treatment with omeprazole in patients with gastroesophageal reflux disease.

Tefera S, Hatlebakk JG, Berstad A.

Division of Gastroenterology, Institute of Medicine, Haukeland Hospital, University of Bergen, Norway.

OBJECTIVE: A trend toward relapse of reflux symptoms and esophagitis during long-term treatment with proton pump inhibitors has been reported. The purpose of this study was to evaluate the existence of tachyphylaxia to the effect of proton pump inhibitors on gastric acidity and gastroesophageal reflux over time. METHODS: A total of 23 patients with reflux esophagitis underwent 24-h intragastric and intraesophageal pH-metry after 7, 90, and 180 days of continued dosing with 20 mg of omeprazole once daily before breakfast. RESULTS: The total median percentages of time gastric pH <4 (interquartile range) were 49% (35-70%), 60% (36-76%), and 42% (26-66%) after 7, 90, and 180 days (p = 0.14). Percentages of time gastric pH <3 were 41%, 54%, and 34%, respectively (p = 0.19). The median percentages of total time esophageal pH <4 were 1.1%, 2.5%, and 1.1%, respectively (p = 0.70). Healing of esophagitis was achieved in 84% of the patients after 6 months. Heartburn improved in six, worsened in three, and was unchanged in 10 patients (p = 0.16). There was no statistical significant relationship between change in esophageal acid exposure and change in severity of heartburn. CONCLUSIONS: A dose of 20 mg of omeprazole once daily consistently controlled patients' symptoms and kept gastric acidity at a stable level over a period of 6 months. There is no evidence of diminution in the effects of 20 mg of omeprazole over time that could indicate the development of tolerance.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11316213&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Omeprazole maintenance therapy for gastroesophageal reflux disease after failure of fundoplication.

Pashankar D, Blair GK, Israel DM.

Division of Gastroenterology, British Columbia's Children's Hospital, Vancouver, Canada.

BACKGROUND: Recurrence of gastroesophageal reflux (GER) in children after failed fundoplication poses a therapeutic challenge. The authors report the experience with long-term omeprazole for children with severe GER after failed fundoplication. METHODS: The authors reviewed the charts of all children who were treated with omeprazole for GER subsequent to failed fundoplication from 1990 to 1999. All underwent endoscopic and clinical assessment of the treatment at baseline, at 3-5 months, at 6-9 months, and annually. RESULTS: Eighteen children presented with GER, after a total of 27 fundoplications. Ten had corrected esophageal atresia, 6 had neurologica impairment, and 2 had hiatal hernia. The mean age of presentation of children with recurrence of GER was 7.8 years, and symptoms of GER occurred 4.9 years (range, 0.6-13) after last fundoplication. Fifteen patients had a mean follow-up of 4.4 years for omeprazole. Ten patients had grade III/IV esophagitis and 5 had grade II esophagitis at presentation after fundoplication. Marked improvement was noted in symptoms of GER and severity of esophagitis while taking omeprazole. Remission of esophagitis was maintained while the patient was taking omeprazole and none had further surgery. There was no recurrence of peptic strictures in eight of nine children on omeprazole, after initial esophageal dilatations. Except for benign gastric polyps in three patients, no clinical adverse effects were observed. CONCLUSIONS: Omeprazole is an effective long-term drug for gastroesophageal reflux disease after failed fundoplication in children. Omeprazole was well-tolerated by all children and should be tried before subsequent surgical intervention.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11321383&dopt=Abstract omeprozole Prilosec