omeprazole, Prilosec
Mobilization of rat stomach ECL-cell histamine in response to short- or long-term treatment with omeprazole and/or YF 476 studied by gastric submucosal microdialysis in conscious rats.

Konagaya T, Bernsand M, Norlen P, Hakanson R.

Department of Pharmacology, Institute of Physiological Sciences, University of Lund, Solvegatan 10, S-223 62 Lund, Sweden.

1. Mobilization of histamine from the ECL cells was monitored by gastric submucosal microdialysis in conscious rats. The ECL cells are known to operate under gastrin control and the purpose of the present study was to examine their in situ response to short-term (12 h) as well as long-term (28 days) hypergastrinaemia, induced by treatment with the proton pump inhibitor omeprazole. 2. Hypergastrinaemia promptly raised the histamine concentration in the microdialysate. The effect was prevented by CCK(2) receptor blockade (YF476). On day 7 of omeprazole treatment the microdialysate histamine concentration reached a peak, five times higher than before treatment. Subsequently (14 and 28 days), less histamine was mobilized. 3. Gastrin infusion (4 h) raised the microdialysate histamine concentration in a dose-dependent manner in fasted rats and freely fed rats and in rats treated with omeprazole for a week. However, while fasted and fed rats responded to low doses of gastrin, the omeprazole-treated rats required large doses of gastrin to respond. 4. When the amount of histamine mobilized was related to the serum gastrin concentration the following EC(50) values could be calculated: fasted rats 2.3 x 10(-10) M, freely fed rats 2.5 x 10(-10) M, omeprazole-treated rats 8.7 x 10(-10) M. The maximal histamine responses in the three groups were 18.4 pmol 4 h(-1)+/-0.8, 21.9 pmol 4 h(-1)+/-1.2 and 68.0 pmol 4 h(-1)+/-3.5, respectively. 5. The results suggest that ECL cells, exposed to a high gastrin concentration for a week, respond with a shift in the receptor-ligand binding affinity from high to low. Apparently, CCK(2) receptors of the ECL cells are subject to dynamic changes with respect to ligand-binding affinity.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11325792&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Pharmacokinetic comparison of omeprazole capsules and a simplified omeprazole suspension.

Song JC, Quercia RA, Fan C, Tsikouris J, White CM.

Department of Pharmacy Services, Hartford Hospital (HH), 80 Seymour Street, Hartford, CT 06102-5037, USA.

The pharmacokinetics of omeprazole delayed-release capsules and a simplified omeprazole suspension (SOS) were studied. Seven healthy volunteers randomly received either one 20-mg omeprazole delayed-release capsule or SOS (omeprazole 20 mg in 10 mL) for seven days before being crossed over to the opposite treatment for seven more days after a two-week washout period. On days 1 and 7, blood samples were drawn at intervals up to 360 minutes after drug administration. Plasma omeprazole concentrations were determined by a validated high-performance liquid chromatographic method, and pharmacokinetic values were determined. Area under the concentration-versus-time curve (AUC) from zero to six hours, AUC from time zero to infinity (AUC0-infinity), and maximum plasma concentration (Cmax) increased by 102%, 113%, and 85%, respectively, after seven days of treatment with the capsule. AUC0-infinity for SOS on day 1 was 58% of that for the capsule (p = 0.0141), and on day 7 it was 49% of that for the capsule (p = 0.0044). AUC0-infinity for SOS increased by 85% from day 1 to 7, but the difference was not significant. Cmax for SOS on day 1 was twice that for the capsule (p = 0.0014), but by day 7 the difference between the two formulations was negligible. Time to Cmax (tmax) for SOS on days 1 and 7 was shorter than for the capsule by 82% (p < 0.0001) and 70% (p < 0.0006), respectively. After one week of therapy, omeprazole absorption was faster and tmax was 70% shorter for SOS than for the capsule formulation, but AUC0-infinity was 49% lower for SOS.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11329761&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Inhibition of drug metabolism in human liver microsomes by nizatidine, cimetidine and omeprazole.

Furuta S, Kamada E, Suzuki T, Sugimoto T, Kawabata Y, Shinozaki Y, Sano H.

Central Research Laboratories, Zeria Pharmaceutical Co., Ltd, Ohsato-gun, Saitama, Japan. ken-taisya zeria.co.jp

1. The inhibitory effects of cimetidine, nizatidine and omeprazole on the metabolic activity of CYP2C9, 2C19, 2D6 and 3A were investigated in human liver microsomes. Both cimetidine and omeprazole inhibited each of the CYP subfamily enzymes; in particular, omeprazole extensively inhibited the hydroxylation of S-mephenytoin (CYP2C19, Ki = 7.1 microM). Nizatidine exhibited no inhibition of any of the CYP isoforms examined. 2. Cimetidine inhibited the hydroxylation of tolbutamide but not of diclofenac, whereas omeprazole inhibited the hydroxylation of diclofenac but not that of tolbutamide. The ability to inhibit CYP2C9 varied with incubation time, as measured by the metabolic rate constant for the substrates. Therefore, suitable substrates and incubation times must be selected in inhibition studies examining metabolic clearance and the mechanism of inhibition of these drugs. 3. Nizatidine did not inhibit the metabolism of cisapride, glibenclamide, benidipine and simvastatin. Omeprazole inhibited the metabolism of cisapride (Ki = 0.4 microM), glibenclamide (11.7 microM) and benidipine (6.5 microM), whereas cimetidine inhibited the metabolism of glibenclamide (11.6 microM). To avoid drug-drug interactions, care needs to be taken to select suitable medicines for co-administration with anti-ulcer drugs.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11334262&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Omeprazole and visual disorders: seeing alternatives.

Lindquist M, Pettersson M, Edwards IR, Sanderson J, Taylor N, Fletcher P, Schou J, Fraunfelder T; DR Signals Analysis Project Team.

The WHO Collaborating Centre for International Drug Monitoring, Uppsala, Sweden.

In the WHO data base, visual disorders reported spontaneously with omeprazole, ranitidine and cimetidine, are very rare in the context of the widespread use of these drugs. There is a maximum reporting rate of severe visual impairment possibly ascribed to i.v. omeprazole of 0.94 reports per million treatment days in one year and in one country, Germany. This gives the worst quantitative case scenario for omeprazole by a single route of administration, to be compared with the worldwide reporting rate of all severe visual disorders by all routes of administration--0.008 reports per million treatment days. Moreover, the reported visual abnormalities have a varied pathophysiological aetiology and their number increased in Germany after the first signal was raised in that country. Thus, apart from a direct causal relationship, solicited reporting artifact is one alternate plausible explanation for the apparent excess of cases of visual disturbance to omeprazole compared with cimetidine and ranitidine. That reporting rates of clinical events on newly marketed drugs are generally higher than with older drugs is a second factor for higher reporting rates with omeprazole. Vasculitis has been suggested as an aetiological factor, but the even lower reporting rate of this reaction makes this an unlikely hypothesis without any other supporting evidence. The authors are unaware of any drug that has caused a vasculities solely affecting the eye. Information on the prevalence of relevant visual disorders in the community would have been of considerable help in interpreting this signal, and a case control study of visual events in relationship to severe illness would be of public health interest, since no data seems to exist concerning this.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15088274&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Assay of omeprazole and omeprazole sulfone by semi-microcolumn liquid chromatography with mixed-function precolumn.

Yim DS, Jeong JE, Park JY.

Department of Pharmacology, Ghil Hospital Emergency Center, Gachon Medical School, Inchon, South Korea. yimds gachon.ac.kr

A column-switching system based on semi-microcolumns was used for direct analysis of omeprazole and omeprazole sulfone in human plasma samples. Plasma samples were injected into a mixed-function (MF Ph-1) column (35 mmx4.6 mm I.D.) to remove proteins and other non-specific peak producing substances from the analyte-containing time zone. The analyte-containing fraction was thereafter transferred to a C-18 semi-microcolumn (250 mmx1.5 mm I.D.) after concentration at the C-18 intermediate column. The absorbance at 302 nm in a ultraviolet (UV) detector was recorded to measure the concentration. The detection limit for omeprazole and omeprazole sulfone in the present method was 10 ng/ml. Interbatch variation (coefficient of variation) of the QC samples spanned less than 10% and intra-batch variation less than 2%. The recovery ratios of omeprazole and omeprazole sulfone were over 98%. The current method can be used as a simpler procedure with similar sensitivity and reproducibility as previously reported methods.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11339292&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Comparison of IY81149 with omeprazole in rat reflux oesophagitis.

Kil BJ, Kim IW, Shin CY, Jeong JH, Jun CH, Lee SM, Kim DY, Huh IH, Sohn UD.

Department of Pharmacology, College of Pharmacy, Chung Ang University, Seoul 156-756, Republic of Korea.

1. This study was aimed at evaluating the effects of IY81149[2-[[(4methoxy-3-methyl)-2-pyridinyl]methylsulfinyl]-5-(1H-pyrrol-1-yl)-1H-benzimidazole], a new proton pump inhibitor, on the development of the surgically induced reflux oesophagitis, on gastric secretion and on lipid peroxidation which is a marker of oxidative stress. Omeprazole was used as a reference drug. We furthermore investigated the influence of quercetin and desferrioxamine (DFO) on the development of the surgically induced reflux oesophagitis in rats on gastric secretion and on lipid peroxidation. 2. IY81149 and omeprazole significantly prevented the development of reflux oesophagitis and gastric secretion in a dose-dependent manner. The ED50 values of IY81149 for inhibition of oesophagitis and volume of gastric secretion were lower than of omeprazole (5.7 vs. 14.2 micromol, 15.3 vs. 24.0 micromol, respectively). IY81149 was also more potent in the acid output inhibition with an ED50 of 6.8 micromol compared with 20.8 micromol of omeprazole. 3. Malonyldialdehyde (MDA) content, the end product of lipid peroxidation, increased significantly in the oesophageal mucosa after the induction of reflux oesophagitis. IY81149 and omeprazole significantly and dose-dependently prevented lipid peroxidation. Quercetin (200 mg kg-1, p.o.) and DFO (800 mg kg-1, i.d.) significantly prevented the development of reflux oesophagitis and inhibited the lipid peroxidation independent of their actions on gastric secretion. 4. This result suggests that IY81149 is comparable with omeprazole in the treatment of reflux oesophagitis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11350494&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Acid regulates inflammatory response in a rat model of induction of gastric ulcer recurrence by interleukin 1beta.

Watanabe T, Higuchi K, Tominaga K, Fujiwara Y, Arakawa T.

Department of Biosignal Analysis, Osaka City University Medical School, Osaka 545-8585, Japan. watanabe med.osaka-cu.ac.jp

BACKGROUND: In a previous study we showed that interleukin 1beta (IL-1beta) caused recurrence of gastric ulcers in rats, and that adhesion molecules (intercellular adhesion molecule 1 and leucocytic beta2 integrins) play a role in this recurrence. Although gastric acid plays an important role in many types of gastric injuries, including peptic ulcer recurrence, the mechanism(s) remains unclear. AIMS: To examine the involvement of gastric acid in induction of ulcer recurrence by IL-1beta, and to investigate the role of gastric acid in inflammatory responses during ulcer recurrence. METHODS: Rats with healed ulcers were used. Rats were given 1 microg/kg IL-1beta intraperitoneally. Another group of rats was given 20 mg/kg omeprazole for three days to inhibit acid secretion, and received IL-1beta 20 hours after the first administration of omeprazole. They were then given 0.15 N HCl or vehicle at 0, 12, 24, and 36 hours after IL-1beta treatment. Some rats were given acid alone at the same time points. Expression of adhesion molecules was examined immunohistochemically and concentrations of IL-1beta and tumour necrosis factor alpha (TNF-alpha) were measured by ELISA in scar tissue 24 hours after IL-1beta treatment. RESULTS: IL-1beta increased expression of adhesion molecules and concentrations of IL-1beta and TNF-alpha in scar tissue by 24 hours after IL-1beta treatment, and nine of 11 healed ulcers had recurred by 48 hours. Omeprazole inhibited the effects of IL-1beta. HCl acid abolished the inhibitory effects of omeprazole. Acid alone affected neither expression of adhesion molecules nor cytokine concentrations, and did not cause recurrence. CONCLUSIONS: Gastric acid is required for recurrence of gastric ulcers caused by IL-1beta, and gastric acid stimulates the inflammatory process in scarred mucosa during ulcer recurrence.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11358894&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Simultaneous intraesophageal impedance and pH measurement of acid and nonacid gastroesophageal reflux: effect of omeprazole.

Vela MF, Camacho-Lobato L, Srinivasan R, Tutuian R, Katz PO, Castell DO.

Department of Medicine, Graduate Hospital, Philadelphia, Pennsylvania 19146, USA.

BACKGROUND & AIMS: Nonacid reflux may explain symptoms in acid-suppressed patients. Simultaneous intraesophageal impedance and pH measurement was used to evaluate the frequencies of postprandial acid and nonacid reflux before and after omeprazole administration. METHODS: Twelve heartburn patients underwent two 2-hour studies of intraesophageal impedance and pH in the right lateral decubitus position after a refluxogenic meal; session 1 without medication, session 2 after 7 days of omeprazole twice daily. Acid and nonacid reflux were quantified. RESULTS: Two hundred seventeen reflux episodes were detected before and 261 after omeprazole treatment (P > 0.05). Percentage of acid reflux decreased (from 45% to 3%, P = 0.02) and nonacid reflux increased (from 55% to 97%, P = 0.03) after omeprazole. Heartburn and acid taste were more commonly linked to acid reflux but were also produced by nonacid reflux. Regurgitation was reported equally in acid and nonacid reflux. Delta(pH) > 1 did not help predict the presence of symptoms during nonacid reflux. CONCLUSIONS: During treatment with omeprazole, postprandial reflux becomes predominantly nonacid. Symptoms are more common with acid reflux but are also produced by nonacid reflux. Simultaneous intraesophageal impedance and pH may be useful in evaluating the role of nonacid reflux in symptoms that persist despite adequate acid suppression.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11375942&dopt=Abstract omeprozole Prilosec