omeprazole, Prilosec
Omeprazole causes delay in gastric emptying of digestible meals.

Benini L, Castellani G, Bardelli E, Sembenini C, Brentegani MT, Caliari S, Vantini I.

Department of Gastroenterology, Rehabilitation Hospital of Valeggio sM, University of Verona, Italy.

We have studied gastric emptying of a solid, realistic meal (800 cal, 15% protein, 45% fat, 40% carbohydrate) in 21 healthy subjects twice, with and without a four-day pretreatment with 40 mg omeprazole. The last dose of the drug was taken 24 hr before the test, to avoid hypothetical nonsecretory side effects of the drug . Gastric emptying was measured by ultrasound of antral diameters. The results show that basal and maximal postprandial antral cross-sectional areas were the same during the two tests. A greater residual distention of the antrum was present throughout the study after the omeprazole treatment, the difference being significant at time 120 and 240. Omeprazole induced a highly significant delay in gastric emptying [control 199.6 (12.6) vs omeprazole 230.9 (12.7) min, mean (1 SEM); P<0.003]. The delay was not due to a prolonged lag phase, but rather to an effect on the slope of the emptying curve. This study shows that in normal subjects omeprazole delays gastric emptying of a digestible solid meal.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8617117&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Comparison between activation of ornithine decarboxylase and histidine decarboxylase in rat stomach.

Ding XQ, Chen D, Rosengren E, Persson L, Hakanson R.

Department of Pharmacology, University of Lund, Sweden.

We compared the responses of rat stomach ornithine decarboxylase (ODC) and histidine decarboxylase (HDC) to food intake, oral treatment with antisecretagogues, NaHCO3, and hypertonic NaCl, antrectomy, intravenous infusion of gastrin-17, the selective cholecystokinin (CCK)-B/gastrin receptor antagonist L-365,260, and the somatostatin analogue RC-160. The serum gastrin concentration and oxyntic mucosal ODC and HDC activities were higher in freely fed rats than in fasted rats. Food intake in fasted rats raised the serum gastrin concentration and the ODC and HDC activities. Ranitidine, omeprazole, and NaHCO3 raised the serum gastrin concentration and activated ODC and HDC. Hypertonic NaCl raised the ODC activity 200-fold, whereas circulating gastrin and HDC activity were increased only moderately. Infusion of gastrin-17 activated HDC but not ODC. L-365,260 prevented the activation of HDC but not of ODC in response to food intake and treatment with omeprazole, NaHCO3, or hypertonic NaCl. Antrectomy prevented the food- and omeprazole-evoked rise in oxyntic mucosal HDC activity but not the rise in ODC activity. RC-160 suppressed HDC activity after food intake and treatment with omeprazole, NaHCO3, or NaCl. In contrast, RC-160 suppressed omeprazole- and NaHCO3-evoked ODC activation but not that evoked by food intake or NaCl. The results support the view that HDC in the oxyntic mucosa is activated by gastrin and suppressed by somatostatin. The induction of ODC is not mediated by gastrin; ODC activation appears to be related to acid inhibition per se or to mucosal maintenance and repair; somatostatin, or rather the lack of it, might contribute to the induction of ODC after acid blockade. The mechanism behind the activation of rat stomach ODC seems to differ depending on the type of stimulus.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8638714&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Omeprazole inhibits growth of gram-positive and gram-negative bacteria including Helicobacter pylori in vitro.

Jonkers D, Stobberingh E, Stockbrugger R.

Department of Gastroenterology, University of Limburg, The Netherlands.

The antibacterial effects of omeprazole (100, 200 and 300 mg/L) were assessed using bacterial growth curves. A dose-related permanent inhibition was seen with actively growing Gram-positive cocci. A reduced and only temporary effect was observed with Gram-negative bacilli. After 1 day the bacterial count of Helicobacter pylori in the presence of omeprazole 200 mg/L was reduced from 10(4) cfu/mL for the control to zero. No synergic or antagonistic interaction of omeprazole with amoxycillin or doxycycline was observed for Escherichia coli and Enterococcus faecalis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8647756&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Effects of pirenzepine on omeprazole-induced gastrin gene expression in rat antral tissues.

Tari A, Hamada M, Kamiyasu T, Fukino Y, Sumii M, Sumii K, Kajiyama G.

Hiroshima Red Cross Hospital, Japan.

Pirenzepine has inhibitory effects on gastrin secretion both in vivo and in vitro. The aim of this study was to determine the mechanism responsible for the suppression of omeprazole-induced hypergastrinemia that occurs with pirenzepine treatment. The effects were measured in rats treated with oral omeprazole plus intraperitoneal pirenzepine or saline once daily for seven days in the antrum. The serum gastrin level increased significantly by more than sixfold with omeprazole treatment; additional treatment with pirenzepine suppressed this increase by 48%. Pirenzepine treatment did not change the level of gastrin mRNA but significantly increased the level of somatostatin mRNA. Combination treatment with omeprazole plus pirenzepine significantly decreased the gastrin mRNA level to half and significantly increased the somatostatin mRNA level up to 1.4-fold of the levels achieved with omeprazole treatment alone. These results suggest that the stimulatory effect of omeprazole on gastrin synthesis is partially blocked by pirenzepine via mediation of somatostatin synthesis in the antrum.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8654146&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
[Is the omeprazole and amoxicillin combination useful in the treatment eradicating Helicobacter pylori in Spain?]

[Article in Spanish]

Gisbert JP, Mur M, Sainz S, Cena G, Martin C, Sainz R, Boixeda D, Mones J.

Servicio de Gastroenterologia, Hospital Ramon y Cajal, Madrid.

AIM: To evaluate the efficiency of omeprazole (20 mg/12 h) plus amoxycillin (1 gr/12 h) in eradicating Helicobacter pylori in duodenal ulcer patients studied in four hospitals in our country. METHODS: One-hundred and four patients (mean age: 49 +/- 16 years, 67% males) attended at four general hospitals in Spain, who had a duodenal ulcer demonstrated by endoscopy. These patients were infected with H. pylori demonstrated by urease test and histologic methods, and in 32 by a breath test and 18 by culture. Omeprazole 20 mg b.i.d. plus amoxycillin 1 gr b.i.d. was administered for 2 weeks. Endoscopy was repeated 1 month after completing therapy, and the aforementioned diagnostic methods were performed again. RESULTS: Eradication was achieved in 29% of cases (n = 30). In multiple logistic regression analysis, duration of ulcer disease was the only variable which correlated with success in H. pylori eradication (chi(2) = 7.2; p = 0.02). Additional variables (age, sex, smoking, pre-treatment with omeprazole, AINEs or H2 antagonist, ulcer size, and antral histologic gastritis) were not correlated with H. pylori eradication. Ulcer healing was demonstrated in 80% of patients (n = 83), and the healing rate was higher when eradication was achieved (97%) than in H. pylori-positive patients (73%) (p < 0.01). Compliance was good in all cases. No adverse effects were observed. CONCLUSSION: Disappointing results were obtained with omeprazole (20 mg b.i.d.) plus amoxycillin (1 gr b.i.d.) on H. pylori eradication. This combination cannot be recommended in our country at the doses employed in this study.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8664080&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Nonlinear kinetics after high-dose omeprazole caused by saturation of genetically variable CYP2C19.

Rost KL, Roots I.

Institute of Clinical Pharmacology, Universitatsklinikum Benjamin Franklin, Berlin, Germany.

Nonlinear kinetics of omeprazole and its metabolites were investigated after treatment with repeated high doses. Extensive metabolizers relating to cytochrome P450 2C19 (CYP2C19) activity received for 1 week either omeprazole at 40 mg/d (n = 14) or 60 mg/d omeprazole twice daily (n = 8). Five poor metabolizers (PMs) received 40 mg/d for 1 week. Comparison of omeprazole plasma kinetics between extensive metabolizers (EMs) and PMs after 40-mg treatment revealed a dominant role of CYP2C19 over cytochrome P450 3A CYP3A in omeprazole metabolism. Comparing the omeprazole doses of 40 mg and 60 mg in eight EMs on day 7 of treatment showed that CYP2C19-dependent plasma clearance of omeprazole and omeprazole sulfone was reduced from 19.0 to 8.4 L/h (P < .001) and from 19.8 to 9.2 L/h (P = .012), respectively. Similarly, formation half-life of 5'-hydroxyomeprazole increased from 0.58 to 1.45 hours (P = .025) with the higher dose. CYP3A-dependent metabolic routes remained unaffected. Thus, high-dose treatment with omeprazole uncovers saturation kinetics for CYP2C19 pathways in EMs, and CYP3A becomes the predominant enzyme of omeprazole elimination. Moreover, these individuals may be at risk for side effects due to high omeprazole concentrations if high-dose omeprazole treatment is combined with drugs inhibiting CYP3A activity.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8675169&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Pharmacokinetics of omeprazole (a substrate of CYP2C19) and comparison with two mutant alleles, C gamma P2C19m1 in exon 5 and C gamma P2C19m2 in exon 4, in Japanese subjects.

Ieiri I, Kubota T, Urae A, Kimura M, Wada Y, Mamiya K, Yoshioka S, Irie S, Amamoto T, Nakamura K, Nakano S, Higuchi S.

Division of Pharmaceutical Science, Kyushu University, Fukuoka, Japan.

The pharmacokinetic profile of omeprazole was examined in 27 healthy Japanese volunteers, and the results were analyzed in relation to genotype for the two mutations, CgammaP2C19m1 in exon 5 and CgammaP2C19m2 in exon 4, associated with the poor metabolizer phenotype. Of the 27 individuals analyzed, 10 were homozygous for the wild-type (wt) allele in both exon 5 and exon 4 (wt/wt; 37.0%, pattern GI), five were heterozygous for the CgammaP2C19m1 (wt/m1; 18.5%, G2), five were heterozygous for the CgammaP2C19m2 (wt/m2; 18.5%, G3), two were heterozygous for the two defects (m1/m2; 7.4%, G4), and five were homozygous for the CgammaP2C19m1 (m1/m1; 18.5%, G5). The allele frequencies of the m1 and m2 mutation were 0.31 and 0.13, respectively. A correlation between the rate of metabolism of omeprazole and genotype was observed. The mean clearance values of omeprazole in patterns G1, G2, G3, G4, and G5 were 1369.0, 332.7, 359.0, 70.8, and 89.5 ml/hr/kg, respectively. The relative area under the serum concentration-time curve (AUC) ratio of omeprazole to 5-hydroxyomeprazole in patterns G1, G2, G3, G4, and G5 was 1:2.8:3.4:16:17.2. A similar relation was observed in the omeprazole/5-hydroxyomeprazole serum concentration ratio, determined 3 hours after drug intake (1:3:4:18.8:20.3). There were significant (p < 0.05 to 0.01) differences in the disposition kinetics of omeprazole between the subjects with patterns G1, G2, and G3 and the subjects with patterns G4 and G5. The results indicate that the 5-hydroxylation pathway of omeprazole is clearly impaired in subjects with m1/m2 and m1/m1.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8681489&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
[Effectiveness of triple therapy to eradicate H. pylori in patients after failed therapy with omeprazole/amoxicillin]

[Article in German]

Zala G, Schwery S, Giezendanner S, Flury R, Wust J, Meyenberger C, Wirth HP.

Departement fur Innere Medizin, der Universitat, Zurich.

Helicobacter pylori (H. pylori) eradication rates with omeperazole/amoxicillin range from 0-90%. The best regimen for retreatment after failure of omeprazole/amoxicillin has not been established so far. The aim of this prospective study was to evaluate the efficacy of triple therapy with bismuth, tetracycline and ornidazole in eradicating H. pylori after failure of omeprazole/amoxicillin. 79 duodenal ulcer patients with H. pylori infection were treated with oral omeprazole (40 mg bid) and amoxicillin solute (750 mg tid) for 10 days. Eradication rate was 28/79 (35%) and was distinctly lower in smokers (> 10 cigarettes/day) vs nonsmokers (10/49 [20%] vs 18/30 [60%], p < 0.001). 37 patients with persistent H. pylori infection in whom omeprazole/amoxicillin had failed agreed to retreatment with triple therapy. Persistence of H. pylori was confirmed by histology (3 antral and 2 gastric body biopsies; H&E, Giemsa), urease test (CLO) and/or H. pylori culture. Patients smoking > 10 cigarettes/day were classified as smokers. Retreatment consisted of oral bismuth-subcitrate 4 x 120 mg/d for 28 days (day 1-28), tetracycline 4 x 500 mg/d and ornidazole 3 x 500 mg/d for 10 days (day 1-10). Control endoscopy was done 30 days after the end of treatment. Criteria for H. pylori eradication was negative urease test, culture and histology. 34/37 patients (6 females/28 males; 39 [23-64] years) completed the study (24/34 smokers, 10/34 nonsmokers). 3/37 patients dropped out because of side effects (n = 1) or incompliance (n = 2). H. pylori subcultures for resistance testing were possible in 32/34 patients: H. pylori was metronidazole-sensitive in 11/32 (1 female, 10 males; 38 [24-55] years; 9 smokers, 2 nonsmokers) and metronidazole-resistant (minimal inhibitory concentration for metronidazole > 8 mg/ml) in 21/32 (5 females, 16 males; 40 [23-64] years; 13 smokers, 8 nonsmokers). The overall H. pylori eradication rate of the triple therapy was 27/34 (79%). H. pylori was eradicated in 19/24 (79%) smokers and in 8/10 (80%) nonsmokers. Eradication rate for metronidazole-sensitive H. pylori was 11/11 (100%) vs 14/21 (67%) for metronidazole-resistant H. pylori (p = 0.012). Triple therapy is effective and safe in eradicating H. pylori in patients after failure of omeprazole/amoxicillin. Smoking had no negative effect on the eradication rate of the triple therapy after failure of omeprazole/amoxicillin. Eradication failures were due to metronidazole-resistance.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8685685&dopt=Abstract omeprozole Prilosec