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Biomedical subjects

D Ouellet

Publications and source records attributed to D Ouellet.

At least 19 recordsLinked to original sources
PubMed2006

Effects of three cytochrome P450 inhibitors, ketoconazole, fluconazole, and paroxetine, on the pharmacokinetics of lasofoxifene.

AIMS: Two studies were conduced to assess the effects of ketoconazole, a CYP3A4/5 inhibitor; fluconazole, a CYP2C9 inhibitor; and paroxetine, a CYP2D6 inhibitor, on lasofoxifene pharmacokinetics. METHODS: The first parallel group study was conducted in 45 healthy postmenopausal women (15 per group) to compare the pharmacokinetics of a single dose of lasofoxifene (0.25 mg) administered alone and in combination with ketoconazole (400 mg daily x 20 days) or fluconazole (400 mg daily x 20 days). Lasofoxifene was administered on day 2 and blood samples were collected serially for up to 456 h postdose (20 days). The second study enrolled 20 healthy postmenopausal women (10 per group) to compare the pharmacokinetics of a single dose of lasofoxifene (0.25 mg) alone and in combination with paroxetine (30 mg qd x 21 days). Lasofoxifene was given on day 8 of paroxetine treatment and blood samples were collected serially for up to 336 h postdose. RESULTS: All subjects completed the study and the treatments were well tolerated. Lasofoxifene C(max) and AUC ratios [90% confidence interval (CI)] with/without ketoconazole were 111% (98.4, 127) and 120% (105, 136), respectively, and were 91.3% (80.3, 104) and 104% (91.4, 118), respectively, with/without fluconazole. Lasofoxifene C(max) and AUC ratios (90% CI) with/without paroxetine were 118% (95.4, 146) and 135% (120, 152), respectively. CONCLUSIONS: Coadministration of potent inhibitors of CYP3A4/5 and CYP2D6, but not CYP2C9, resulted in a moderate increase in lasofoxifene exposure. No dosage adjustment should be required when lasofoxifene is coadministered with ketoconazole, fluconazole, paroxetine or other agents that inhibit these CYP enzymes.

Adult↗
PubMed2004

Purification, characterization and amino acid sequencing of divergicin M35: a novel class IIa bacteriocin produced by Carnobacterium divergens M35.

Carnobacterium divergens M35, isolated from a commercial sample of frozen smoked mussels, produces a new bacteriocin, divergicin M35, a class IIa bacteriocin. Divergicin M35 is sensitive to pronase-E, alpha-chymotrypsin and proteinase K, but not to trypsin and withstands thermal treatments up to 121 degrees C for 30 min. Divergicin M35 was extracted from the culture supernatant of C. divergens M35 using an SP-Sepharose cation-exchange column, desalted and purified on a C18 Sep-Pack column and further purified by reverse phase-high pressure liquid chromatography. This procedure allowed the recovery of 10% of the bacteriocin present in the culture supernatant with purity higher than 99%. Divergicin M35 had a molecular mass of 4518.75 Da as determined by mass spectrometry, a pI value of 8.3 and positive net charge (+3). The amino acid sequence of divergicin M35 was found to consist of 43 amino acid with four cysteine residues (Cys10, 15, 25, 43) and showed 80.5% homology with divercin V41 (80.5%) and 80.0% with bavaricin MN. Divergicin M35 showed powerful antilisterial activity, especially against Listeria monocytogenes and was also active against carnobacteria but not against strains of Lactococcus, Lactobacillus, Enterococcus, Bifidobacteria and Escherichia. Divergicin M35 production began in late exponential phase and reached a maximum activity of 65,000 AU/ml in early stationary phase. Initial broth pH, Tween 80 and acetate did not affect C. divergens M35 growth or divergicin production. This bacteriocin may be a potential tool for inhibiting L. monocytogenes in seafood products that do not usually undergo an adequate heat treatment.

Amino Acid Sequence↗
PubMed2001

Population pharmacokinetics of gabapentin in infants and children.

PURPOSE: To characterize gabapentin pharmacokinetics in infants and children using a population approach and to identify important demographic and/or physiologic determinants of gabapentin disposition. METHODS: Gabapentin was administered in single doses of 10 mg/kg (N=48 healthy subjects, age 1 month-12 years) or in multiple doses of 10-65 mg/kg per day (N=205 patients with epilepsy, age 2 months-13 years) at 08:00, 14:00, and 20:00. Serial concentration-time data from the healthy subjects were combined with sparse data obtained in patients and were modeled using NONMEM. RESULTS: Gabapentin oral clearance (l/h) was directly related to creatinine clearance (ml/min) with a slope of 0.116. The slope of the relationship was 36% greater in blacks than in subjects of other races. When oral clearance was normalized for body weight, young children (<5 years) had higher and more variable values than older children. Volume of distribution was related to body weight and appeared to differ between subjects and patients. Intersubject variability was approximately 30% for oral clearance and volume of distribution and was larger for the absorption rate constant and lag time. Residual variability, a measure of intrasubject variability and measurement error, was smaller in subjects than in patients. CONCLUSIONS: On a weight basis, 33% larger doses would be required in younger children (<5 years) to achieve the same exposure as older children.

Acetates↗
PubMed2001

Estimation of allantoin flux using continuous infusion of [14C]allantoin: sensitivity to plasma loading with unlabelled allantoin.

Allantoin net flux through the plasma allantoin compartment was determined in sheep given a roughage diet by means of a continuous infusion of [4,5-14C]allantoin for 17 h. Unlabelled allantoin was infused intravenously during the last 7 h of the tracer infusion to increase the allantoin flux by approximately 75 %. When unlabelled allantoin was infused, the specific radioactivity of allantoin in plasma and urine declined exponentially to approach a lower plateau some 2-3 h later. The estimate of net flux during the infusion of unlabelled allantoin, estimated from blood plasma and urine, was on average 79 and 90 % of expected values. Expected values of allantoin net flux during infusion of unlabelled allantoin were calculated as the sum of allantoin net flux pre-loading plus the known rate of infusion of the allantoin load. It is probable that endogenous allantoin synthesis was decreased by the infusion of allantoin: allosteric inhibition of uricase appears a plausible explanation for this observation, and for lower estimates of net flux. Appearance of labelled allantoin-C in ruminal or blood bicarbonate was negligible. Our results indicate that net flux of allantoin through blood plasma is a good predictor of the entry rate of allantoin into the primary compartment and should be a better predictor of rumen microbial outflow than urinary allantoin excretion. However, measurements of allantoin-specific radioactivity, during continuous infusion, should be taken after a period of 24 h, at which time the true plateau specific radioactivity value of allantoin in plasma would be attained.

Allantoin↗
PubMed2001

Single-dose gabapentin pharmacokinetics and safety in healthy infants and children.

Gabapentin (Neurontin) is a gamma-aminobutyric acid analogue indicated in adults for adjunctive treatment of partial seizures with or without secondary generalization. Two studies were conducted to determine the single-dose pharmacokinetics of gabapentin in healthy subjects age 1 month to 12 years and to guide dose selection in safety and efficacy trials in pediatric patients. Forty-eight subjects were given single oral doses of gabapentin (10 mg/kg) while fasting. Enrollment was homogeneously distributed throughout the age range. Plasma samples were drawn predose and then serially for 24 hours postdose. Single doses of gabapentin were well tolerated by healthy pediatric subjects. Plots of pharmacokinetic parameters versus age suggested significant differences between younger (1 month to < 5 years) and older (> or =5 to 12 years) subjects. Mean area under the plasma concentration-time curve from zero to infinity (AUC(0-infinity)) was 25.6 microg x h/mL in younger subjects and 36.0 microg x h/mL in older subjects (p < 0.001). Corresponding mean peak plasma concentrations (Cmax) were 3.74 and 4.52 microg/ml (p < 0.05). Oral clearance (normalized for body weight) was 7.40 and 4.41 mL/min/kg in younger subjects and older subjects, respectively (p < 0.001). It was concluded that children between 1 month and < 5 years of age require approximately 30% higher daily doses of gabapentin than those > or =5 to 12 years of age.

Acetates↗
PubMed2000

Population pharmacokinetics of pemetrexed disodium (ALIMTA) in patients with cancer.

PURPOSE: To evaluate the population pharmacokinetics of pemetrexed disodium in cancer patients enrolled in four different open-label, multicenter, nonrandomized phase II studies. METHODS: Pemetrexed disodium was administered as a 10-min intravenous infusion (600 mg/m2) every 21 days. A total of four blood samples were to be collected each cycle per patient (n= 103 patients) during cycles 1 and 3. Plasma concentration-time data were analyzed by nonlinear mixed-effect modeling using NONMEM to estimate pemetrexed disodium pharmacokinetic parameters (mean, and between- and within-patient variability) as well as relationships between the pharmacokinetic parameters and various patient-specific factors (demographic and physiologic data). RESULTS/CONCLUSIONS: The pharmacokinetics of pemetrexed disodium were best characterized by a two-compartment model with initial distribution and terminal elimination half-lives of 0.63 h and 2.73 h, respectively. The typical value of systemic clearance (CL) in liters per hour included a relationship to creatinine clearance (CrCL) with a slope of 0.0292. Typical values of central volume (V(c)), distributional CL (Q), and peripheral volume (V(p)) were 11.3 1, 3.21 l/h, and 5.20 l, respectively. Between-patient variability was 19.6%, 15.6%, and 21.7% for CL, V(c), and V(p), respectively. A combined additive/proportional error model was used to describe residual variability, with a coefficient of variation of 23.7% for the proportional component and a standard deviation of 0.0410 microg/ml for the additive component. Significant patient-specific factors on CL were calculated CrCL, body weight, and to a lesser extent alanine transaminase and folate deficiency. Gender and body weight were significant factors on V(c) while both body surface area and albumin were significant factors on V(p). In conclusion, population pharmacokinetic modeling revealed relationships between pharmacokinetic parameters and various patient specific factors.

Adult↗
PubMed1999

Comparison of different methods to evaluate population dose-response and relative potency: importance of interoccasion variability.

Different mixed-effects models were compared to evaluate the population dose-response and relative potency of two albuterol inhalers. Bronchodilator response was measured after ascending doses of each inhaler in 37 asthmatic patients. A linear mixed-effects model was developed based on the approach proposed by Finney for the evaluation of bioassay data. A nonlinear mixed-effects (Emax) model with interindividual and interoccasion variability (IOV) in the different pharmacodynamic parameters was also fit to the data. Both methods produced a similar estimate of relative potency. However, the estimate of relative potency was 22% lower with the nonlinear mixed-effects model if IOV was not taken into account. Monte Carlo simulations based on a similar study design demonstrated that more biased and variable estimates of ED50 and relative potency were obtained when the nonlinear mixed-effects model ignored the presence of IOV in the data. Furthermore, the linear mixed-effects model that did not account for IOV produced confidence intervals for relative potency that were too narrow and thus could lead to erroneous conclusions. These problems were avoided when the estimation model could account for IOV. Results of the simulations were consistent with those of the experimental data. Although the linear or the nonlinear mixed-effects model may be used to evaluate population dose-response and relative potency, there are important differences in the assumptions made by each method.

Administration, Inhalation↗
PubMed1998

Pharmacokinetic interaction between ritonavir and clarithromycin.

BACKGROUND: Because ritonavir, a human immunodeficiency virus (HIV) protease inhibitor, and clarithromycin, a macrolide antibiotic used in the treatment of disseminated infection caused by Mycobacterium avium complex, are likely to be administered concurrently for treatment of patients with HIV and acquired immunodeficiency syndrome (AIDS), the drug interaction potential of these 2 agents was evaluated. Both clarithromycin and ritonavir are metabolized to a significant extent through cytochrome P450-mediated biotransformation and are potential inhibitors of these enzymes. OBJECTIVE: To evaluate the pharmacokinetic effects of concomitant administration of multiple doses of ritonavir and clarithromycin. METHODS: This was an open-label, randomized, 3-period crossover study. Ritonavir alone (200 mg every 8 hours), clarithromycin alone (500 mg every 12 hours), and ritonavir and clarithromycin in combination were administered to 22 healthy volunteers. Blood samples were collected on day 4 for determination of ritonavir, clarithromycin, and its metabolite 14-(R)-hydroxyclarithromycin. RESULTS: Ritonavir practically completely inhibited the formation of 14-(R)-hydroxyclarithromycin. The mean area under the plasma concentration-time curve (AUC) for clarithromycin increased by 77% with concomitant ritonavir, and the harmonic mean terminal half-life increased from 5 hours to 14 hours. Statistically significant increases in peak plasma concentration (31%) and minimum plasma concentration (182%) were also observed. The effect of concomitant clarithromycin administration on ritonavir pharmacokinetics was statistically significant but small, with a 12.5% increase in mean AUC and a 15.3% increase in peak plasma concentration. The terminal half-life increased from 3.47 to 3.87 hours with concomitant clarithromycin. CONCLUSIONS: No adjustment of the ritonavir dose is necessary when administered with clarithromycin. In addition, no changes in clarithromycin dose are warranted in patients with normal renal function.

AIDS-Related Opportunistic Infections↗
PubMed1998

Effect of ritonavir on the pharmacokinetics of ethinyl oestradiol in healthy female volunteers.

AIMS: To assess the effects of the protease inhibitor ritonavir on the pharmacokinetics of ethinyl oestradiol in healthy female volunteers. METHODS: This was an open-label, single centre study in 23 subjects who received two single doses of oral contraceptive containing 50 microg ethinyl oestradiol on Day 1 (alone) and on Day 29 during concomitant ritonavir. Each subject received 16 days of every 12 h doses of ritonavir from Day 15 through Day 30. Blood samples were collected for serum ethinyl oestradiol concentrations for 48 h after each dose and for plasma ritonavir on Day 29 at 0 and 4 h postdose. RESULTS: Statistically significant decreases in ethinyl oestradiol mean Cmax (-32%) and mean AUC (-41%), and a statistically significant increase in the mean terminal elimination rate constant (+31%) were observed during concomitant ritonavir. The harmonic mean terminal half-life decreased from 17 h to 13 h during concomitant ritonavir. No statistically significant change was noted in tmax. The ratios of means (95% confidence intervals) for Cmax and AUC were 0.682 (0.612-0.758) and 0.595 (0.506-0.694), respectively. The changes in ethinyl oestradiol pharmacokinetics were consistent with an increase in clearance from enzymatic induction of glucuronidation and/or cytochrome P450 hydroxylation. Mean steady-state ritonavir concentrations of 6.5 and 13.4 microg ml(-1) were observed at 0 and 4 h postdose, respectively. CONCLUSIONS: Considering the extent of the decrease in ethinyl oestradiol concentrations, the use of alternate contraceptive measures should be considered when ritonavir is being administered.

Adult↗
PubMed1998

Effect of fluoxetine on pharmacokinetics of ritonavir.

The potential interaction between fluoxetine, a known inhibitor of cytochrome P-450 isoform 2D6 (CYP2D6), and ritonavir, a human immunodeficiency virus type 1 protease inhibitor, was evaluated in this open-label study. Sixteen male and female subjects ranging in age from 18 to 40 years completed the study. Subjects received single doses of 600 mg of ritonavir on days 1 and 10. On study days 3 to 10, all subjects received 30 mg of fluoxetine every 12 h for a total of 16 consecutive doses. Serial blood samples for determination of ritonavir concentrations in plasma were collected after the administration of ritonavir on days 1 and 10. A limited number of blood samples for determination of fluoxetine and norfluoxetine concentrations were collected after administration of the morning dose on day 10. A statistically significant increase (19%) in the ritonavir area under the concentration-time curve (AUC) was observed with concomitant fluoxetine administration, with individual changes ranging from -12 to +56%. The change in the ritonavir AUC with concomitant fluoxetine administration was positively correlated with the norfluoxetine 24-h AUC (AUC24) (r2 = 0.42), the norfluoxetine/fluoxetine AUC24 ratio (r2 = 0.53), and the fluoxetine elimination rate constant (r2 = 0.65), with larger increases in the ritonavir AUC tending to occur with higher norfluoxetine concentrations and higher fluoxetine elimination rate constants. The effect of fluoxetine appeared to be larger in subjects with the CYP2D6 wt/wt genotype. There was little or no effect on the time to maximum drug concentration (Cmax) in serum, Cmax, and the elimination rate constant of ritonavir with concomitant fluoxetine administration. Considering the magnitude of the change observed, no ritonavir dose adjustment is recommended during concomitant fluoxetine administration.

Adolescent↗
PubMed1997

Oxidative metabolism of clarithromycin in the presence of human liver microsomes. Major role for the cytochrome P4503A (CYP3A) subfamily.

In vitro studies were conducted to identify the hepatic cytochrome P450 (CYP) protein(s) involved in the oxidative metabolism of [14C]clarithromycin (CLAR) in the presence of native human liver microsomes. The identity of the two major CLAR metabolites present in microsome incubates, 14-(R)-hydroxy-CLAR and N-desmethyl-CLAR, was confirmed by MS. Over the CLAR concentration range of 1.0-140 microM, the rate of CLAR 14-(R)-hydroxylation (KM = 48 +/- 17.7 microM; Vmax = 206 +/- 76 pmol/min/mg protein; Vmax/KM = 4.2 +/- 0.21 microliters/min/mg; mean +/- SD, N = 3 livers) and N-demethylation (KM = 59.1 +/- 24.0 microM; Vmax = 189 +/- 52.0 pmol/min/mg protein; Vmax/KM = 3.3 +/- 0.53 microliters/min/mg) conformed to monophasic (saturable) Michaelis-Menten kinetics and was highly correlated (r = 0.90-0.92; p < 0.001; N = 11) with CYP3A-selective erythromycin N-demethylase activity. Ketoconazole (< or = 2.0 microM) or troleadomycin, CYP3A-selective inhibitors, markedly decreased (> or = 99%) the formation of both metabolites, whereas inhibitors selective of other CYP forms were relatively ineffective (< or = 10% inhibition). In agreement with chemical inhibitor studies, CLAR metabolism was only detectable with human B-lymphoblastoid microsomes containing cDNA-expressed CYP3A4 (vs. CYP2C19, CYP2C9, CYP2D6, CYP1A2, CYP2E1, or CYP2A6). Furthermore, the apparent KM characterizing the 14-(R)-hydroxylation and N-demethylation of CLAR in the presence of insect cell microsomes containing cDNA-expressed CYP3A4 (KM = 18-63 microM) was similar to that obtained with native human liver microsomes. Based on the results of this study, it is concluded that the 14-(R)-hydroxylation and N-demethylation of CLAR is primarily mediated by one or more members of the human liver CYP3A subfamily.

Anti-Bacterial Agents↗
PubMed1996

[O-methyl 14C]naproxen O-demethylase activity in human liver microsomes: evidence for the involvement of cytochrome P4501A2 and P4502C9/10.

Cytochrome P450 (CYP) activity in human liver microsomes was measured after the O-demethylation of [O-methyl 14C]naproxen (NAPase). The formation of [14C]formaldehyde in the presence of microsomes was described by an apparent KM(1) and Vmax(1) of 0.16 +/- 0.09 mM and 4.1 +/- 2.8 nmol HCHO/min/mg protein (mean +/- SD; N = 5 different livers), respectively, over a relatively wide naproxen concentration (5-1600 microM) range. With two sets of microsomes, a high KM NAPase component was also detected (mean KM2 = 2.7 mM; mean Vmax2 = 23 nmol HCHO/min/mg). As expected, the O-demethylation of naproxen (0.4 mM) was found to be highly correlated with tolbutamide hydroxylase (TOLase) activity in a panel of human liver microsomes (r = 0.82, p < 0.01, N = 10) and was inhibited (32-54%) by a number of purported CYP2C (CYP2C9/10) inhibitors/substrates (e.g. phenytoin, sulfaphenazole, tienilic acid, tolbutamide, and ibuprofen). Only marginal decreases in activity (< or = 14%) were observed with inhibitors of other CYP proteins. However, NAPase activity was also found to correlate significantly with CYP1A2 [ethoxyresorufin O-deethylase (ERODase)] activity (r = 0.68, p < 0.05, n = 11). In addition, the reaction was inhibited (36-75%, N = 11 different livers) by furafylline (FURA), a CYP1A2-selective mechanism-based inhibitor. The effect of FURA and tienilic acid was additive, leading to 90 +/- 4.2% inhibition of NAPase activity. FURA-inhibited activity also significantly correlated with ERODase activity (r = 0.78, p < 0.01, N = 11), whereas tienilic acid-inhibited activity correlated with TOLase activity (r = 0.63, p < 0.05, N = 10). In human B-lymphoblast microsomes, cDNA-expressed CYP1A2 exhibited relatively high activity (KM = 0.25 mM; Vmax = 24 nmol/min/nmol CYP), when compared with CYP2A6, CYP2D6, CYP2E1, CYP2B6, and CYP3A4. The kinetic parameters for reconstituted purified human liver microsomal CYP2C9 (KM = 0.43 mM; Vmax = 11 nmol/min/nmol CYP) were comparable with those of CYP1A2. It is concluded that the O-demethylation of naproxen (< or = 0.4 mM) is catalyzed by CYP2C subfamily members (CYP2C9/10) and CYP1A2 in human liver microsomes.

B-Lymphocytes↗
PubMed1994

Heparinized saline versus normal saline in maintaining patency of the radial artery catheter.

OBJECTIVE: To compare the ability of normal versus heparinized saline infusion to maintain patency of the radial artery catheter used for monitoring or multiple blood sampling. DESIGN: Randomized double-blind trial. SETTING: A university-affiliated hospital. PATIENTS: All 108 patients admitted to the surgical intensive care unit who required radial arterial line catheters. Excluded were patients who required emergency admission, those who refused to give consent, those who needed anticoagulants, thrombolytic or platelet therapy, those whose cannulation site was other than the radial artery, inadvertent discontinuation of the arterial line or incomplete data collection. This resulted in a sample of 78 adults, randomized according to date of admission. INTERVENTIONS: Forty patients admitted on odd-numbered dates received heparinized normal saline (2 units/mL), and 38 patients admitted on even dates received normal saline, both as continuous flush solutions. MAIN OUTCOME MEASURES: Measurement of radial artery flow and pressure before and after cannulation, and catheter patency during cannulation. RESULTS: The type of flush solution did not adversely affect the radial artery or the hand in any measurable way. Catheter blockage occurred in three patients receiving heparinized saline and seven patients receiving normal saline as the flush solution (p = 0.06). At 96 hours of cannulation, 92% of the catheters in the heparinized saline group were patent compared with 74% in the normal saline group. Intra-arterial blood pressure was inaccurate compared with the brachial cuff pressure in 6 patients in the heparinized saline group compared with 14 patients in the normal saline group (p < 0.03). CONCLUSIONS: There is no significant difference between flushing with normal saline and heparinized saline in the maintenance of radial arterial line patency. However, the use of a continuous heparinized flush solution in pressurized arterial lines is beneficial in that it results in greater accuracy of blood pressure monitoring than normal saline infusion.

Adult↗
PubMed1993

Model for selecting quality standards for a salad bar through identifying elements of customer satisfaction.

Continuous quality improvement is the new requirement of the Joint Commission on Accreditation of Healthcare Organizations. This means that meeting quality standards will not be enough. Dietitians will need to improve those standards and the way they are selected. Because quality is defined in terms of the customers, all quality improvement projects must start by defining what customers want. Using a salad bar as an example, this article presents and illustrates a technique developed in Japan to identify which elements in a product or service will satisfy or dissatisfy consumers. Using a model and a questionnaire format developed by Kano and coworkers, 273 students were surveyed to classify six quality elements of a salad bar. Four elements showed a dominant "must-be" characteristic: food freshness, labeling of the dressings, no spills in the food, and no spills on the salad bar. The two other elements (food easy to reach and food variety) showed a dominant one-dimensional characteristic. By better understanding consumer perceptions of quality elements, foodservice managers can select quality standards that focus on what really matters to their consumers.

Consumer Behavior↗
PubMed1993

A roadmap for the novice researcher.

This article outlines the research process as it applies to nurses in clinical practice. While the topic seems intimidating at first, by questioning clinical practice and maintaining an open mine, nurses can generate the enthusiasm and commitment necessary to conduct their own research. First, a nursing research issue worthy of investigation needs to be identified and thoroughly reviewed in the literature. The nurse next needs to bring together an appropriate research team and develop a formal research proposal. The team then submits the proposal through the organizational structure that grants approval and provides funding. Once the study has been implemented and the data collection is complete, the research team must decide on the best method of disseminating the research findings to nursing colleagues. This last important step helps to expand and build nursing's professional body of knowledge, and ensures that current nursing practice is based on valid research findings.

Clinical Nursing Research↗
PubMed1990

Omeprazole: a novel antisecretory agent for the treatment of acid-peptic disorders.

Omeprazole represents the first agent of a unique class of acid inhibitory drugs, the proton pump inhibitors. Omeprazole inhibits basal gastric acid secretion, as well as gastrin-, histamine-, or pentagastrin-stimulated secretion, which results in decreased gastric acidity, decreased gastric acid output, and decreased gastric volume. Omeprazole is acid labile, necessitating its oral administration in an enteric-coated formulation. Bioavailability appears to be dose-dependent, with more drug being absorbed with increasing dosage as well as after repeated dosing. This is probably secondary to decreased gastric acidity and, therefore, less degradation of the administered drug. Despite its relatively short half-life (1-2 h), omeprazole's pharmacologic action is prolonged. Clinical trials have shown omeprazole to be at least as effective as histamine2-receptor antagonists in the treatment of gastric ulcers, duodenal ulcers, gastroesophageal reflux, and Zollinger-Ellison syndrome. Adverse reactions have been minimal. Omeprazole has been approved by the Food and Drug Administration for short-term therapy of severe erosive esophagitis, poorly responsive symptomatic gastroesophageal reflux disease, and long-term management of Zollinger-Ellison syndrome.

Animals↗