omeprazole, Prilosec
Intragastric pH during treatment with omeprazole: role of Helicobacter pylori and H. pylori-associated gastritis.

Verdu EF, Armstrong D, Idstrom JP, Labenz J, Stolte M, Borsch G, Blum AL.

Division of Gastroenterology, CHUV, Lausanne, Switzerland.

BACKGROUND: Omeprazole treatment produces lower intragastric pH values 4 weeks after cure of Helicobacter pylori infection than before. We therefore investigated the effect of healing H. pylori-associated gastritis on intragastric pH in the presence and in the absence of omeprazole therapy. METHODS: Before and on day 8 of omeprazole, 20 mg once daily, 24-h intragastric pH-recordings were performed in 14 subjects with H. pylori infection and repeated 4 and 52 weeks after cure of infection. Gastritis severity in corpus and antrum was graded by using a modified Sydney system. RESULTS: In the absence of omeprazole administration, median 24-h pH values before cure did not differ from those 4 and 52 weeks after cure. On day 8 of omeprazole administration, 24-h pH values were much higher before cure (median, 5.15; 95% confidence interval (CI), 4.3-6.0) than 4 weeks (3.6; 2.1-4.4; P < 0.001) and 52 weeks after cure (3.0; 2.1-4.4; P < 0.001). The activity of corpus and antral gastritis was not associated with the magnitude of H+ change induced by omeprazole. CONCLUSION: The increased pH produced by omeprazole during H. pylori infection is likely to be due to neutralizing substances produced by H. pylori and not to H. pylori-induced gastritis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8976005&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Partial regression of Barrett's esophagus by long-term therapy with high-dose omeprazole.

Malesci A, Savarino V, Zentilin P, Belicchi M, Mela GS, Lapertosa G, Bocchia P, Ronchi G, Franceschi M.

Universita di Milano, Dipartimento di Medicina Interna, Italy.

BACKGROUND: Barrett's esophagus is mainly regarded as an acquired condition related to increased gastroesophageal reflux. Thus it is conceivable that abolition of acid reflux would lead to its regression. The aim of this study was to assess whether long-term treatment with high-dose omeprazole (60 mg/day) produces a consistent control of gastric acid production and normalizes the esophageal acid exposure, thus reducing the length of Barrett's epithelium. METHODS: Fourteen patients (8 men and 6 women, mean age 52 years) with histologic diagnosis of columnar epithelium longer than 3 cm in the distal part of the esophagus were enrolled and began receiving 60 mg of omeprazole in a single daily morning dose. Before therapy and after 6 and 12 months of therapy, all patients had endoscopy with four-quadrant biopsies at 2 cm intervals. A 24-hour esophagogastric pH recording was performed at entry and after 10 days, 6 months, and 12 months of treatment in all patients. RESULTS: The initial length of Barrett's epithelium (4.5 +/- 1.9 cm) was significantly reduced after 6 months (3.1 +/- 1.1; p < 0.01) and 12 months (2.1 +/- 1.6; p < 0.005) of treatment. Values were significantly lower at 12 than at 6 months (p < 0.03). The 24-hour mean gastric pH after 10 days (5.89 +/- 0.58), 6 months (5.71 +/- 0.55), and 12 months (5.54 +/- 0.76) of therapy was always higher (p < 0.001) than the basal level (1.9 +/- 0.49). No significant difference in gastric pH was seen over the treatment period. The 24-hour mean percent of time in which pH in the esophagus was below 4.0 decreased significantly (p < 0.001) from a basal rate of 29.4% to 3.5%, 3.0%, and 4.9% in the various time intervals of therapy. There was a normalization of esophageal acid exposure in all patients but two. CONCLUSIONS: It can be concluded that the antisecretory effect of 60 mg/day of omeprazole is consistent and is kept constant throughout the entire 1-year treatment period. The consequent normalization of esophageal acid exposure in almost all patients in our series led to a partial, but significant, regression in the length of Barrett's epithelium.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8979061&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Nasogastric omeprazole: effects on gastric pH in critically Ill patients.

Balaban DH, Duckworth CW, Peura DA.

Division of Gastroenterology and Hepatology, University of Virginia, Charlottesville, USA.

OBJECTIVE: The efficacy of omeprazole administered by the nasogastric route has not been adequately studied. We sought to determine whether nasogastrically administered omeprazole could effectively maintain an intragastric pH greater than 4.0 in patients hospitalized in a medical intensive care unit. METHODS: Patients were considered eligible for the study if they had a nasogastric feeding tube in place and had not received omeprazole, antacids, or histamine-2 blockers in the 5 days preceding study enrollment. Exclusionary criteria included active GI bleeding or a mean baseline gastric pH greater than 4.0. Patients served as their own controls during a 24-h lead-in period, during which baseline intragastric pH was measured by gastric aspirate. Omeprazole, 20 or 40 mg, was administered once daily with water through a nasogastric tube. Intragastric pH was measured every 4-8 h for a maximum of 3 days following drug administration. RESULTS: Twenty patients were considered eligible for the study; 10 were excluded because of an elevated baseline gastric pH (n = 8) or because proper gastric aspirates could not be obtained (n = 2). The mean baseline intragastric pH in four patients receiving omeprazole 20 mg q.d. was 2.4 +/- 1.1 and increased to 3.7 +/- 1.6 after drug administration (p = 0.013). The mean baseline intragastric pH in six patients receiving omeprazole 40 mg q.d. was 2.8 +/- 0.8 and increased to 5.7 +/- 1.1 after drug administration (p < 0.001). The percentage of intragastric pH values greater than 4.0 after drug administration was 34.2% in patients receiving omeprazole 20 mg q.d. and 84.7% in those receiving omeprazole 40 mg q.d. CONCLUSIONS: Nasogastric omeprazole 40 mg q.d. is effective in maintaining an intragastric pH greater than 4.0 in critically ill patients. The nasogastric administration of omeprazole offers a cost-effective therapeutic option for acid suppression in patients at risk for stress mucosal ulceration.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8995942&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
CYP2C19 genotype and phenotype determined by omeprazole in a Korean population.

Roh HK, Dahl ML, Tybring G, Yamada H, Cha YN, Bertilsson L.

Department of Medical Laboratory Sciences and Technology, Karolinska Institute, Huddinge Hospital, Sweden.

Omeprazole (20 mg orally) was given to 103 healthy Korean subjects and blood was taken 3 h after administration. The plasma concentration ratio of omeprazole and hydroxyomeprazole, used as an index of CYP2C19 activity, was bimodally distributed. Thirteen subjects (12.6%) were identified as poor metabolizers (PMs) with an omeprazole hydroxylation ratio of 6.95 or higher. Among the 206 CYP2C19 alleles, CYP2C19*2 and CYP2C19*3 were found in 43 alleles (21%) and 24 alleles (12%), respectively. Twelve subjects (12%) carried two defect alleles (*2/*2, *2/*3 or *3/*3), 43 subjects (42%) were heterozygous for a mutated (*2 or *3) and a wild type (*1) allele, and the remaining 48 subjects (47%) were homozygous for the wild type allele. The distributions of the metabolic ratio between these three genotype groups were significantly different (Kruskal-Wallis test: p < 0.0001). The genotypes of 19 additional Korean PMs has been identified in a previous mephenytoin study. From a total of 32 PMs, 31 were genotypically PMs by analysis of the CYP2C19*2 and *3 alleles and only one PM subject was found to be heterozygous for the *1 and *2 alleles. At present it cannot be judged whether this subject has a defective allele with a so-far unidentified mutation or a true wild type allele. We thus confirm a high incidence (12.6%) of PMs of omeprazole in Koreans and of the 32 Korean PMs 97% could be identified by the genotype analysis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9014204&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Pilot study of the oral omeprazole test for reflux laryngitis.

Metz DC, Childs ML, Ruiz C, Weinstein GS.

Department of Medicine, University of Pennsylvania, PA 19104, USA.

BACKGROUND: Gastroesophageal reflux disease occasionally presents with laryngeal symptoms. Such patients are often referred for a gastroenterology evaluation. This study was designed to determine whether an empiric trial of high-dose omeprazole therapy could reliably identify patients with reflux laryngitis and thus obviate the need for a gastroenterology workup. METHODS: Patients were evaluated with a history, physical examination, esophageal manometry, upper endoscopy, and 24-hour pH-metry for determination of the presence of absence of underlying gastroesophageal reflux disease and then received an empiric trial of oral omeprazole therapy (20 mg twice daily for 1 month). A positive omeprazole test result was defined as resolution of all laryngeal symptoms on completion of the empiric trial of therapy. RESULTS: Two patients were classified as having no reflux, and eight were classified as having reflux. Omeprazole test results were positive in six patients. Five of six had reflux, but one patient had no evidence for reflux. Omeprazole test results were negative in four patients. Three of four had reflux, and one did not. Despite the absence of antisecretory therapy, laryngeal symptoms did not recur in either patient without reflux during follow-up. Laryngeal symptoms were managed in two of the three patients with reflux who had negative omeprazole test results and who were using inhalers in combination with histamine H2 receptor antagonist therapy for their reflux disease. One patient with reflux who had a negative omeprazole test result responded to higher doses of omeprazole, and the five patients with reflux who had positive omeprazole test results all responded to continuation of omeprazole. CONCLUSIONS: The omeprazole test may be useful in confirming the suspicion of reflux laryngitis in patients suspected of having this disease after an otolaryngology evaluation. However, there is a potential for false-positive and false-negative test results. A gastroenterology evaluation may aid in the identification of false-positive test results by documenting the absence of reflux in certain responders.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9018256&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Does concurrent acute ethanol ingestion during omeprazole therapy affect pituitary gonadal axis in male subjects?

Mokshagundam SL, Minocha A.

University of Louisville, Kentucky, USA.

OBJECTIVE: Literature suggests that both ethanol and omeprazole may affect the endocrine system. We studied the effect of concurrent use of ethanol and omeprazole on the pituitary gonadal axis in healthy males. METHODS: Serum testosterone, luteinizing hormone, and follicle stimulating hormone levels were assessed in a fasting state before and after ingestion of 0.5 g/kg bodyweight of ethanol. Subjects then received omeprazole therapy (20 mg 2x/d for one week) followed by assessment of hormone levels before and after ethanol ingestion as done previously. RESULTS: Total testosterone levels before and after ethanol at baseline declined an average of 46.6 ng/dL (n = 8; p = NS). The testosterone levels before and after ethanol following omeprazole therapy rose an average of 55.4 ng/dL (n = 8; p = NS). There was no significant difference in the change of ethanol induced testosterone concentrations as a result of omeprazole therapy. Similarly the free testosterone, follicle stimulating hormone, and luteinizing hormone were also not affected by ethanol or omeprazole alone or in combination. CONCLUSIONS: We conclude that omeprazole and/or acute ingestion of ethanol do not affect the pituitary gonadal axis in healthy male subjects.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9022653&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Inhibition by omeprazole of proguanil metabolism: mechanism of the interaction in vitro and prediction of in vivo results from the in vitro experiments.

Funck-Brentano C, Becquemont L, Lenevu A, Roux A, Jaillon P, Beaune P.

Clinical Pharmacology Unit, Saint-Antoine University Hospital-School of Medicine, Paris, France.

Both the antimalarial prodrug proguanil and the gastric proton pump inhibitor omeprazole are substrates for cytochrome P450 (CYP)2C19 and CYP3A. However, the relative contribution of each enzyme to proguanil bioactivation to cycloguanil and to the metabolism of omeprazole, as well as their potential to interact, remains to be examined. The bioactivation of proguanil to its active metabolite cycloguanil was studied in vitro in human liver microsomes and in vivo in 12 healthy subjects, in the absence and in the presence of omeprazole. The formation of cycloguanil from proguanil exhibited biphasic kinetic behavior in four of six human livers, indicating that at least two enzymes are responsible for this metabolic step. Cycloguanil formation activity did not correlate with immunoreactive CYP3A4 content or with CYP3A4 activity, as measured by testosterone 6beta-hydroxylation, suggesting that CYP3A4 plays a limited role in cycloguanil formation. Furthermore, troleandomycin (10 microM) inhibited only 10 to 17% of cycloguanil formation at proguanil concentrations of 100 and 500 microM. At a proguanil concentration of 20 microM, omeprazole at 10 microM inhibited cycloguanil formation in vitro by 47 +/- 59%. These in vitro results were consistent with the results of our in vivo study in healthy subjects, which showed a 32 +/- 11% decrease in proguanil apparent oral clearance and a 65 +/- 8% decrease in proguanil partial metabolic clearance to cycloguanil in the presence of omeprazole (both P < .001). We conclude that in vitro studies of proguanil metabolism and interactions are predictive of in vivo situations, that CYP2C19 is the main enzyme responsible for proguanil bioactivation to cycloguanil and that omeprazole inhibits this biotransformation in vitro and in vivo by inhibiting this enzyme.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9023285&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Effect of omeprazole on the course of associated esophagitis and laryngitis.

Jaspersen D, Weber R, Hammar CH, Draf W.

Department of Gastroenterology, Academic Hospital Fulda, Germany.

Esophagitis has increasingly been implicated as a cause of chronic laryngitis and there is some evidence that gastro-esophageal reflux disease (GERD) is more common in patients with laryngitis. The aim of this study was to evaluate whether patients with esophagitis and laryngitis responded to treatment with omeprazole. Of 74 consecutive patients with endoscopically proven GERD, 21 had laryngitis. These 21 patients with associated esophagitis and chronic laryngitis were treated for 4 weeks with omeprazole 40 mg per day. After 2 weeks of treatment and at the conclusion of the study, 2 weeks later, esophagoscopy and laryngoscopy were performed and the patients responded to a questionnaire on their symptoms. The follow-up period was 1 year. Twenty-one of the 74 patients (28.4%) had esophagitis (grade I, n = 12; grade II, n = 9) and associated laryngitis (grade I, n = 14; grade II, n = 7). The severity of the esophagitis accorded with the severity of the laryngitis. After 2 weeks' treatment with omeprazole, both the esophageal and the laryngeal symptoms had improved in all 21 patients. Endoscopically, the healing rates were 62% for esophagitis and 33.3% for laryngitis. At the end of the study period, at 4 weeks, all patients were symptom-free and the esophagitis and laryngitis had healed completely. No patient suffered from drug-induced side effects. Patients with associated laryngitis and esophagitis should be given adequate anti-reflux therapy. Both the laryngeal and esophageal symptoms improved with the omeprazole treatment, suggesting that reflux was the underlying etiology.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9027637&dopt=Abstract omeprozole Prilosec