omeprazole, Prilosec
Extent and variation of omeprazole prescribing in an elderly population of Ontario.

McBride JE, Pater JL, Dorland JL, Lam YM.

Kingston General Hospital, Ontario, Canada.

OBJECTIVE: To determine the extent of omeprazole prescribing in the senior population of Ontario over a 1-year period; the variation in omeprazole prescribing for this population according to age group, gender, and geographic region: and the extent of inappropriate prescribing of omeprazole for this population. DESIGN: Retrospective drug utilization review of prescription drug insurance claims. DATA SOURCE: The Ontario Drug Benefit (ODB) program claims database. OUTCOME MEASURES: The following outcomes were measured: the proportion of seniors in Ontario who received a prescription for omeprazole from April 1, 1992 to March 31, 1993: effects of age group, gender, and geographic region of residence on omeprazole prescribing; and the extent of inappropriate omeprazole prescribing according to the ODB criteria for use. Prescribing of omeprazole was defined as inappropriate if a first-line antiulcer drug (i.e., histamine2-receptor antagonist) was not prescribed within 1-6 months of the first prescription claim for omeprazole. RESULTS: A total of 29,936 seniors in Ontario received omeprazole from April 1, 1992 to March 31, 1993 (2.53 recipients per 100 eligible population). The age-gender group most frequently prescribed omeprazole was women 65-74 years, followed by women and men 75 years or older, and then men 65-74 years. Omeprazole prescribing varied widely among the 48 provincial counties (range of 1.66 recipients per 100 eligible population to 4.52 recipients per 100 population, p < 0.001). There was no evidence of a clustering effect in omeprazole prescribing at the county level. Prescribing of omeprazole was considered to be inappropriate for 80.5% of recipients. CONCLUSIONS: This study demonstrated the ineffectiveness of the ODB limited-use program in controlling omeprazole prescribing. Further study should be done to examine determinants of variation in prescribing by geographic region.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9101000&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Efficacy of omeprazole one year after cure of Helicobacter pylori infection in duodenal ulcer patients.

Labenz J, Tillenburg B, Peitz U, Borsch G, Idstrom JP, Verdu E, Stolte M, Blum AL.

Department of Internal Medicine and Gastroenterology, Elisabeth Hospital Essen, Germany.

OBJECTIVE: We have previously shown that, in duodenal ulcer patients, pH control by omeprazole is less pronounced after cure of Helicobacter pylori infection. The present study was designed to test the hypothesis that this response to omeprazole persists 1 yr after cure of H. pylori infection. METHODS: In 12 duodenal ulcer patients, intragastric acidity was measured with a glass electrode during treatment with omeprazole (20 mg) once daily before, and 4-6 wk and 1 yr after, cure of H. pylori infection. H. pylori infection was assessed by [13C]urea breath test, culture, histology (Warthin Starry stain), and rapid urease test. RESULTS: Cure of H. pylori infection resulted in a lowered pH during omeprazole treatment. This effect persisted after 1 yr. Median 24-h gastric pH before H. pylori treatment was 5.6; 4-6 wk after cure of the infection it was 2.9 (p = 0.003), and 1 yr after cure of the infection it remained unchanged (pH = 2.5; p = 0.5). Accordingly, twice as much time was spent above pH 3 and pH 4 before H. pylori treatment than 1 or 12 months after cure (percent of time > or = pH 3: 82.7 vs. 49.7 vs. 43.1; percent of time > or = pH 4: 72.7 vs. 38.3 vs. 26.4). CONCLUSION: In duodenal ulcer patients, cure of H. pylori infection resulted in a marked rapid and persistent decrease of the pH increasing effect of omeprazole. Therefore, H. pylori is a determinant of the pH achieved in response to omeprazole treatment in duodenal ulcer patients.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9128302&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Different effects of omeprazole and Sch 28080 on canine cerebrospinal fluid production.

Javaheri S, Corbett WS, Simbartl LA, Mehta S, Khosla A.

VA Medical Center, Department of Medicine, University of Cincinnati College of Medicine, OH 45220, USA.

We investigated the effects of omeprazole and Sch 28080, a more specific and a more potent inhibitor of K+,H+-ATPase than omeprazole, in canine cerebrospinal fluid (CSF) production. CSF production was measured by ventriculocisternal perfusion (VCP) technique in three groups (n = 10 in each group) of anesthetized, paralyzed and mechanically ventilated dogs. Group I served as control, Sch 28080 (10(-4) mol/l of synthetic CSF) was added to VCP in group II, and omeprazole (10(-5) mol/l of synthetic CSF) was added to VCP in group III, after baseline control CSF production had been determined at 15, 30, 45, and 60 min. Comparing the three groups, the mean baseline values for CSF production did not differ significantly. However, the percent decreases in CSF production in the omeprazole treated group were 26 +/- 17 and 24 +/- 13 at 210 and 225 min, which were significantly more than the respective values in the control group. Percent decrease in CSF production in Sch 28080 was not significantly different from that in the control group. We conclude that in the canine model, physiological doses of omeprazole decrease CSF production by about 26%. However, the effect is independent of the K+,H+-ATPase activity, since Sch 28080 which is more potent than omeprazole did not significantly affect CSF production.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9134992&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Regulation of dioxin receptor function by omeprazole.

Dzeletovic N, McGuire J, Daujat M, Tholander J, Ema M, Fujii-Kuriyama Y, Bergman J, Maurel P, Poellinger L.

Department of Cell and Molecular Biology, Medical Nobel Institute, Karolinska Institute, S-171 77 Stockholm, Sweden.

The intracellular dioxin (aryl hydrocarbon) receptor mediates signal transduction by dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin) and related environmental pollutants and functions as a ligand-activated transcription factor. In this study we have examined the effects on dioxin receptor function of a potentially novel ligand, omeprazole, which is widely clinically used as a gastric anti-ulcer drug. In primary human hepatocytes omeprazole potently induced cytochrome P4501A1 mRNA expression, whereas this effect was not detected in mouse primary hepatocytes. In human hepatoma cells omeprazole was found to induce transcription of reporter genes via the xenobiotic response element that is recognized by the ligand-activated dioxin receptor. In contrast, the human dioxin receptor was not activated by omeprazole upon expression in a receptor-deficient mouse hepatoma cell line. In a reconstituted yeast (Saccharomyces cerevisiae) model system, however, both the mouse and human dioxin receptors were potently activated by omeprazole. Although omeprazole failed to displace dioxin in in vitro ligand binding assays, a residue within the ligand binding domain that is critical for dioxin binding in vitro was also critical for omeprazole responsiveness in vivo. Consistent with this observation, both omeprazole and dioxin responsiveness of the dioxin receptor was inhibited in mutant yeast cells expressing low levels of the molecular chaperone hsp90 that is critical for ligand binding activity. The sulfoxide group that is essential for formation of a planar conversion product of omeprazole was found to be critical for dioxin receptor activation. Taken together, these data suggest that omeprazole represents a precursor for a novel class of dioxin receptor agonists that are bona fide dioxin receptor ligands but generated in a strictly species-specific manner.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9139728&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Nonencapsulated, intact omeprazole granules effectively suppress intragastric acidity when administered via a gastrostomy.

Sharma VK, Heinzelmann EJ, Steinberg EN, Vasudeva R, Howden CW.

Department of Internal Medicine, and W. J. B. Dorn Veterans' Affairs Medical Center, University of South Carolina School of Medicine, Columbia 29203-6808, USA.

Because of its acid-labile nature, omeprazole is usually administered as encapsulated enteric-coated granules. The gelatin capsule and acid-resistant coating are essential for effective drug absorption and optimal bioavailability. OBJECTIVE: This study tested the effectiveness of nonencapsulated, intact omeprazole granules in suppressing intragastric acidity when administered through a gastrostomy. METHODS: Fourteen male patients with established gastrostomies underwent a baseline 24-h intragastric pH monitoring study while off any acid-suppressing medication. Via the gastrostomy, they then received 7 days of dosing with 20 mg omeprazole as intact granules in orange juice. Twenty-four-hour intragastric pH monitoring was repeated on the seventh day. RESULTS: Mean intragastric pH during the baseline study was 1.8 (+/- SD 0.7). This pH increased to 4.9 +/- 0.8 with omeprazole granules (p < 0.0001). Median intragastric pH rose from 1.3 to 5.3 (p < 0.0001). During the baseline study, intragastric pH was above 3 for 21.2 +/- 14.1%, above 4 for 14.9 +/- 11.0%, and above 5 for 9.5 +/- 8.4% of the 24-h recording period. Corresponding values after 7 days of omeprazole were 80 +/- 15.1%, 72.5 +/- 16.3%, and 59.1 +/- 16.6% (p < 0.0001 for each comparison with pretreatment values). CONCLUSION: Omeprazole effectively suppresses intragastric acidity when given through a gastrostomy tube as nonencapsulated, intact granules.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9149199&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Lack of weight-based dose dependency and intraindividual variability of omeprazole for CYP2C19 phenotyping.

Kim MJ, Nafziger AN, Zhang Y, Sellers EM, Gaedigk A, Bertino JS Jr.

Clinical Pharmacology Research Center, Bassett Healthcare, One Atwell Road, Cooperstown, NY 13326-1394, USA.

To determine if dose dependency occurs with 2 weight-based single doses of omeprazole in a phenotyping study, as well as to quantitate 3-month intraindividual variability of CYP2C19 activity, 24 Caucasian subjects with body weights from 45 to 66 kg and 67 to 90 kg received single oral 30-mg and 40-mg doses of omeprazole, respectively. Female subjects were phenotyped during the mid-follicular and mid-luteal phases of their menstrual cycles for 3 complete cycles. Male subjects were phenotyped every 14 days for 12 weeks. Subjects with a body weight between 45 and 66 kg received an additional 40-mg omeprazole single dose on visit 7. The 2-hour postdose plasma concentration ratio of omeprazole to 5-hydroxyomeprazole was used as a measure of CYP2C19 activity. The percent coefficient of variation (CV%) of omeprazole phenotyping ranged from 6.3% to 51.3% (median = 18.5%, interquartile range = 14.8%-23.5%). Weight-based single doses of omeprazole for CYP2C19 phenotyping did not exhibit dose dependency. Therefore, a weight-based approach may improve the quantitation of omeprazole/metabolites.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15317824&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
The effect of long-term omeprazole on the glucose-hydrogen breath test in elderly patients.

Hutchinson S, Logan R.

Portsmouth Healthcare NHS Trust, Queen Alexandra Hospital, UK.

OBJECTIVE: to test whether omeprazole taken for longer than 1 month causes an increase in the rate of small bowel bacterial overgrowth in elderly subjects. SUBJECTS: 44 elderly people, 22 taking omeprazole, 22 not taking omeprazole or H2 receptor antagonists. MAIN OUTCOME MEASURES: rate of positive glucose-hydrogen breath tests; anthropometric measures and blood tests reflecting malabsorption. RESULTS: there was no difference in the rate of positive tests between those taking omeprazole (45%) and those not taking it (59%). The omeprazole group had significantly lower serum albumin concentrations. There was no difference in body mass index, mid-arm circumference, arm fold thickness, adjusted calcium concentration or haemoglobin levels. CONCLUSIONS: omeprazole does not cause increased bacterial shall bowel overgrowth in elderly subjects.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9177664&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Altered pharmacokinetics of omeprazole in cystic fibrosis knockout mice relative to wild-type mice.

Tallman MN, Ali SY, Smith PC.

Department of Drug Delivery and Disposition, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.

The cftr(tm1Unc)-knockout (CF-KO) mouse is being evaluated as a model of increased drug clearance noted clinically in patients with cystic fibrosis (CF). This study investigated whether CF-KO mice exhibited altered omeprazole pharmacokinetics compared with wild-type mice. Clinical observations have suggested reduced responses to omeprazole in CF children, which may reflect alterations in bioavailability or clearance. Omeprazole was dosed intravenously and orally in a crossover fashion to age-matched CF-KO and wild-type male and female mice. The mean terminal half-life of approximately 6 min was found across genotype and gender groups. Blood to plasma ratio estimates for omeprazole were similar across genders and genotypes with a mean value of 0.69. Omeprazole blood clearance (Cl(b)) was significantly higher in both male (190 ml/min/kg) and female (168 ml/min/kg) CF-KO mice compared with wild-type controls of the same gender (73 ml/min/kg for males and 100 ml/min/kg for females). The distributional volume of omeprazole in CF-KO mice was also statistically higher than in control genotypes. Bioavailability estimates were similar between CF-KO and wild-type females but were unavailable for male mice, due to the large variability in plasma concentrations after oral administration and the difficulty estimating the area under the plasma curve when the terminal half-life suggested absorption rate-limited disposition. Potential mechanisms for the pharmacokinetic differences observed with omeprazole in CF-KO mice may be increased hepatic blood flow or an up-regulation of hepatic transporters. These results may provide support for using the CF-KO mouse as a model for the altered disposition of drugs in CF.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15319328&dopt=Abstract omeprozole Prilosec