omeprazole, Prilosec
Pharmacodynamic interactions of omeprazole with CNS active drugs in rats.

Chandrashekhar SM, Chakrabarti A, Garg SK.

Department of Pharmacology, Postgraduate Institute of Medical Education & Research, Chandigarh.

A pharmacodynamic interactional study with omeprazole was undertaken in rats. Omeprazole (7 mg/kg, orally once daily for 14 days) significantly prolonged pentobarbitone (30 mg/kg, ip) induced hypnosis while it had no effect on haloperidol (1 mg/kg, ip) induced catalepsy or morphine (5 mg/kg, ip) induced analgesia models in rats. The study highlighted the fact that dynamic interaction with omeprazole was selective.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7705876&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Induction of cytochrome P4501A by smoking or omeprazole in comparison with UDP-glucuronosyltransferase in biopsies of human duodenal mucosa.

Buchthal J, Grund KE, Buchmann A, Schrenk D, Beaune P, Bock KW.

Institute of Toxicology, University of Tubingen, Germany.

Drug-metabolizing enzymes were investigated in duodenal biopsy specimens. Cytochrome P4501A (CYP1A) activity was determined by measuring 7-ethoxyresorufin O-deethylase (EROD) activity in biopsies from 20 smokers (3-30 cigarettes per day), 21 nonsmokers, and 10 nonsmokers receiving omeprazole treatment (20-60 mg/day for at least 1 week). Omeprazole is known to act as a polycyclic aromatic hydrocarbon (PAH)-type inducer in humans. EROD activity was found to be significantly induced in smokers and omeprazole-treated patients, with medians of 2.1 and 1.1 pmol.min-1.mg protein-1, respectively, compared with 0.5 pmol.min-1.mg protein-1 in nonsmokers. Immunoblot analysis substantiated that EROD activity was correlated with CYP1A protein. In contrast, UDP-glucuronosyltransferase (UGT) activity towards 4-methylumbelliferone (an overlapping substrate of several constitutive and inducible UGTs) was not significantly affected. The results demonstrate CYP1A induction by omeprazole and by constituents of cigarette smoke in the human duodenum and support the utility of duodenal biopsies to monitor CYP1A induction by PAH-type inducers.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7720765&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Omeprazole/Antacid-powder suspension-Santarus: omeprazole/sodium bicarbonate powder-Santarus, SAN 05.

[No authors listed]

Santarus Inc. is developing an immediate-release formulation of omeprazole in combination with an antacid (sodium bicarbonate) as a powder for suspension, known as Acitreltrade mark [SAN 05] and also as Rapinex powder for oral suspension. This omeprazole powder suspension will be used to treat gastrointestinal haemorrhage, gastro-oesophageal reflux disease, heartburn and peptic ulcers.Acitreltrade mark is based on technology licensed from the University of Missouri. Santarus have also licensed technology from Tulane and North Carolina Universities relating to potential treatments for gastrointestinal (GI) diseases.Santarus has licensed exclusive, worldwide rights to patent applications covering specific combination formulations of proton pump inhibitors (PPIs) and antacids for treating various upper GI diseases and disorders.Santarus plans to license the development, distribution and marketing rights of omeprazole powder for oral suspension 20 mg outside the US, to one or more well established pharmaceutical companies.The US FDA has requested that Santarus pursue a name other than Rapinex for the product. Santarus is currently discussing potential alternative names for the product with the FDA.Santarus announced positive results in August 2003 from a phase III trial comparing oral Acitrel (Rapinex 40 mg) with intravenous cimetidine in preventing upper GI bleeding in 359 critically ill adult patients. Santarus has also completed an open-label clinical trial in 243 patients, including 97 patients with gastric ulcers, evaluating the safety of this omeprazole 40 mg powder suspension for an 8-week period.In connection with the NDA for omeprazole powder suspension 40 mg, Santarus provided notice to the NDA holder for Prilosec delayed-release capsules and related patent owners that omeprazole powder suspension 40 mg does not infringe currently listed patents for Prilosec or that those patents are invalid.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15563239&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Inhibition of food passage by omeprazole in the chicken.

Mabayo RT, Furuse M, Okumura J.

Laboratory of Animal Nutrition, School of Agriculture, Nagoya University, Japan.

The effect of omeprazole, a proton pump inhibitor, on the forward passage of the crop contents of chicks receiving 20% medium chain or long chain triacylglycerol was studied. Medium chain triacylglycerol significantly delayed the crop emptying of chicks compared with long chain triacylglycerol. Omeprazole also significantly inhibited passage from the crop of the long chain triacylglycerol meal. Application of omeprazole induces achlorhydria and consequently hypergastrinemia but chicken gastrin lower than 100 nmol/kg did not delay crop emptying. The addition of hydrochloric acid (HCl) to the diet reversed the action of omeprazole on the crop emptying of chicks. We conclude, then, that omeprazole delayed the crop emptying in chicks as a consequence of inhibition of acid secretion, although the mediator is not gastrin.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7737310&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Antisecretory and antiulcer effects of YM020, a new H+,K(+)-ATPase inhibitor, in rats and dogs.

Yuki H, Kamato T, Nishida A, Ohta M, Shikama H, Yanagisawa I, Miyata K.

Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Ibaraki, Japan.

We examined the effects of YM020 (3-cyanomethyl-2-methyl-8-[(3-methyl-2-butenyl)oxy]-imidazo[1,2- a]pyridine), a novel H+,K(+)-ATPase inhibitor, on gastric acid secretion and experimental gastroduodenal lesions in rats and dogs. Intraduodenal, subcutaneous and oral YM020 inhibited basal gastric acid secretion in pylorus-ligated rats with ED50 values of 9.1, 9.1 and 9.5 mg/kg, respectively. Oral pretreatment with YM020 5 hr before ligation still suppressed acid secretion, with a potency a little less than that of omeprazole. In anesthetized dogs, intravenous YM020 inhibited histamine-, methacholine- and pentagastrin-induced gastric acid secretion with ED50 values of 0.05, 0.01 and 0.08 mg/kg, respectively. In Heidenhain pouch dogs, although oral YM020 (3 mg/kg) inhibited histamine-induced acid secretion, acid output returned to control levels faster than in dogs treated with omeprazole. Oral YM020 inhibited the formation of water-immersion restraint stress-, indomethacin-, absolute ethanol-, 0.7 N hydrochloric acid- and cysteamine-induced gastric or duodenal lesions with ED50 values of 2.9, 4.3, 2.0, 11.7 and 8.4 mg/kg, respectively. Moreover, subcutaneous YM020 also suppressed the formation of ethanol- and HCl-induced gastric lesions. These results suggest that YM020 has an antisecretory effect almost the same as or 2 to 3 times weaker than those of omeprazole and that its duration is not as long as that of omeprazole in rats and dogs. Furthermore, YM020 possesses a cytoprotective effect and the mechanism of YM020 may be different to that of omeprazole.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7745846&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Observation of gastric glandular cysts in the corpus mucosa of the stomach under omeprazole treatment.

Stolte M, Bethke B, Seifert E, Armbrecht U, Lutke A, Goldbrunner P, Rabast U.

Institut fur Pathologie, Klinikum Bayreuth.

In patients undergoing long-term treatment with omeprazole, tiny gastric polyps, described histologically as glandular cysts, have occasionally been reported. We report on a further nine patients (5 women and 4 men) undergoing omeprazole treatment who developed endoscopically visible and histologically verified glandular cysts. Eight patients were on long-term treatment with omeprazole for reflux oesophagitis, and the glandular cysts were observed between 8 and 60 months after the start of treatment. In one patient with an NSAID-induced ulcer, a tiny polyp was found only three weeks after initiation of treatment. None of the patients had Helicobacter pylori-associated gastritis. The cysts, which measured between 0.25 and 0.7 mm in diameter, were mostly lined with flattened parietal and chief cells, but in three cases also with foveolar epithelium, so that they could not be reliably distinguished from Elster's gastric glandular cysts. These glandular cysts are harmless, and do not require further diagnostic or therapeutic measures. They probably develop spontaneously independently of the omeprazole therapy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7754645&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Omeprazole and dry mouth.

Teare JP, Spedding C, Whitehead MW, Greenfield SM, Challacombe SJ, Thompson RP.

Gastrointestinal Laboratory, Rayne Institute, St Thomas' Hospital, London, UK.

BACKGROUND: Omeprazole causes irreversible inhibition of the hydrogen/potassium adenosine triphosphatase enzyme, leading to a marked reduction in both acid secretion and volume of gastric juice. Reported side-effects include nausea, vomiting, diarrhoea, constipation, and headache. We report the development of dry mouth during omeprazole therapy. METHODS: We have identified six patients taking omeprazole for more than 6 weeks who complained of a dry mouth. Salivary production was measured as whole salivary flow produced over a 10-min period spat into a collecting vessel and as 5% citric acid-stimulated parotid salivary flow collected with a Lashley cup device placed over the parotid duct. Flow rates were evaluated both during and after cessation of treatment. Saliva produced was then cultured for microbes. RESULTS: Four of the six had subnormal parotid or whole salivary flow rates on treatment that recovered after stopping treatment. The increase after treatment was marked in four. Significant amounts of Candida albicans grew from the saliva of the three patients with the lowest salivary flows; one saliva also grew Staphylococcus aureus. CONCLUSION: Salivary flow is reduced in some patients treated with omeprazole, returning to normal after cessation of treatment. This reduction may predispose to opportunistic infection, particularly in the edentulous.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7770709&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
The hydroxylation of omeprazole correlates with S-mephenytoin metabolism: a population study.

Balian JD, Sukhova N, Harris JW, Hewett J, Pickle L, Goldstein JA, Woosley RL, Flockhart DA.

Department of Medicine and Pharmacology, Georgetown University Medical Center, Washington, DC 20007, USA.

We compared omeprazole and mephenytoin as probes for the CYP2C19 metabolic polymorphism. Single oral doses of omeprazole (20 mg) or mephenytoin (100 mg) were administered at least 1 week apart to 167 healthy volunteers. Mephenytoin metabolism was measured using the amount of 4'-hydroxymephenytoin and the S/R ratio of mephenytoin in an 8-hour urine collection. Omeprazole hydroxylation was measured using the ratio of omeprazole to 5'-hydroxyomeprazole in serum 2 hours after dosing. All three methods separated poor- or extensive-metabolizer phenotypes with complete concordance. Omeprazole hydroxylation correlated with the S/R ratio of mephenytoin in extensive metabolizers (r2 = 0.681; p < 0.001). Genotyping tests showed that six poor metabolizers of omeprazole were homozygous for a single base pair mutation in exon 5 of CYP2C19. These results support the hypothesis that omeprazole 5'-hydroxylation cosegregates with the CYP2C19 metabolic polymorphism.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7781266&dopt=Abstract omeprozole Prilosec