esomeprazole, Nexium
Esomeprazole-Induced Central Fever with Severe Myalgia (April).

Grattagliano I, Portincasa P, Mastronardi M, Palmieri VO, Palasciano G.

Section of Internal Medicine, Department of Internal Medicine and Public Medicine, University Medical School of Bari, Bari, Italy.

OBJECTIVE: To report a case of central fever associated with severe myalgia following esomeprazole. CASE SUMMARY: A 64-year-old man presented with intense cephalalgia; severe, diffuse myalgia; and fever (>40 degrees C) after esomeprazole initiation for treatment of gastritis. Five hours after ingestion of the first esomeprazole pill (40 mg), the patient developed fever associated with cephalalgia and myalgia. This condition lasted about 40 hours and disappeared spontaneously. Symptoms partially responded to acetaminophen. Four days later, the patient received a second dose of esomeprazole 40 mg. Subsequently, 4 hours later, fever (>40 degrees C), headache, and difficulty in the movement of all parts of the body recurred. Neurologic examination was negative except for a minor state of disorientation. All reflexes were normal or slightly decreased. No skin lesions or breathing difficulty was noted. Routine blood tests were normal. Again, symptoms resolved spontaneously about 40 hours later. DISCUSSION: The temporal connection between esomeprazole intake and the onset of fever suggests a probable causal link, as confirmed by the Naranjo probability scale. However, the pathogenic mechanism remains unclear. Considering that esomeprazole is able to cross the blood-brain barrier, its peak serum concentration is reached 90-180 minutes after oral administration, and its serum half-life is approximately 2 hours, we assume that the appearance of fever with accompanying neurologic and muscular symptoms might result from the drug interference with the hypothalamic regulatory center of body temperature. CONCLUSIONS: Hyperpyrexia of central origin associated with intense cephalalgia and myalgia may occur as an adverse effect of esomeprazole therapy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15741426&dopt=Abstract esomeprozole Nexium



esomeprazole, Nexium
The effect of the area under the plasma concentration vs time curve and the maximum plasma concentration of esomeprazole on intragastric pH.

Junghard O, Hassan-Alin M, Hasselgren G.

AstraZeneca R&D Molndal, 431 83 Molndal, Sweden. ola.junghard astrazeneca.com

OBJECTIVE:The aim of this study was to create a useful model of the effect of the area under the plasma concentration vs time curve (AUC) and the maximum plasma concentration (C(max)) of esomeprazole on intragastric pH, measured as the percentage of total time with intragastric pH above 4 (%pH>4) during a 24-h period. METHODS: The evaluation is based on esomeprazole data from two crossover studies. In the first study ( n=36), intragastric pH and plasma concentrations were measured on day 5 of repeated once-daily 20-mg and 40-mg doses of esomeprazole during fasting conditions. In the second study ( n=24), measurements were made on days 1 and 5 of repeated once-daily dosing with 40 mg of esomeprazole under fasting and fed conditions. A model was applied in which the logistic function of %pH>4 was assumed to be linearly dependent on log-transformed AUC and C(max). The effects of repeated dosing and of fed relative to fasting conditions were included in the model, and the interindividual variation in %pH>4 was accounted for. RESULTS: The effect of the pharmacokinetic variables AUC and C(max) of esomeprazole on %pH>4 can be adequately described by a model using a logistic function for %pH>4 and a normally distributed error. In this model, log-transformed AUC and C(max) were both statistically significant. The model showed that for a fixed AUC, a decrease in C(max) gives an increase in %pH>4. A decrease in AUC, keeping C(max) fixed, gives a decrease in %pH>4, but a simultaneous decrease in C(max) and AUC will result in a less pronounced decrease in %pH>4. The model may be used for predicting differences in %pH>4 between two formulations, based on assessments of AUC and C(max). Repeated dosing gave an increased %pH>4, where approximately half of the increase stemmed from increased AUC and C(max), and the rest could be attributable to the persistent blockade of the proton pumps. Food intake reduced AUC and C(max) but had no obvious effect on %pH>4, which is explained by a prolonged time period with quantifiable plasma concentrations. CONCLUSION: The effect of the pharmacokinetic variables AUC and C(max) of esomeprazole on %pH>4 can be adequately described by a model using a logistic function for %pH>4 and a normally distributed error.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12389067&dopt=Abstract esomeprozole Nexium



esomeprazole, Nexium
Antimicrobial activity of esomeprazole versus omeprazole against Helicobacter pylori.

Gatta L, Perna F, Figura N, Ricci C, Holton J, D'Anna L, Miglioli M, Vaira D.

Department of Internal Medicine and Gastroenterology, University of Bologna, via Massarenti 9, 40138 Bologna, Italy.

OBJECTIVE: Esomeprazole is an enantiomorph of omeprazole, which inhibits gastric acid secretion more effectively than omeprazole. As proton pump inhibitors also exert an antibacterial activity, we aimed to compare esomeprazole and omeprazole for their antimicrobial activity against Helicobacter pylori in vitro. METHODS: We studied 52 H. pylori isolates obtained from gastric biopsies and inoculated onto agar plates containing the acid-converted drugs at different concentrations. The minimal concentrations that inhibited the growth of 50% and 90% of isolates were defined as MIC(50) and MIC(90). RESULTS: The MIC(50) and MIC(90) of esomeprazole were 16 and 32 mg/L; and those of omeprazole were 32 and 64 mg/L. Overall, 63.5% of isolates showed the same susceptibility to both drugs; 17 isolates were two- to 64-fold more susceptible to esomeprazole and two isolates were two-fold more susceptible to omeprazole. CONCLUSIONS: The increased antimicrobial activity in vitro of esomeprazole against H. pylori could contribute to improving the outcome of the eradication treatment of such an infection.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12562719&dopt=Abstract esomeprozole Nexium



esomeprazole, Nexium
Gateways to clinical trials.

Bayes M, Rabasseda X, Prous JR.

Prous Science, Barcelona, Spain. mbayes prous.com

Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abetimus sodium, adalimumab, alefacept, alemtuzumab, almotriptan, AMGN-0007, anakinra, anti-CTLA-4 Mab, L-arginine hydrochloride, arzoxifene hydrochloride, astemizole, atazanavir sulfate, atlizumab; Belimumab, BG-9928, binodenoson, bosentan, botulinum toxin type B, bovine lactoferrin, BufferGel; Caspofungin acetate, ciclesonide,cilomilast, ciluprevir, clofarabine, CVT-3146; Darbepoetin alfa, desloratadine, diflomotecan, doripenem, dronedarone hydrochloride, drotrecogin alfa (activated), DT388-GM-CSF, duloxetine hydrochloride, E-5564, efalizumab, enfuvirtide, esomeprazole magnesium, estradiol acetate, ETC-642, exenatide, exisulind, ezetimib; Febuxostat; Gallium maltolate, ganirelix acetate, garenoxacin mesilate, gefitinib; H11, HuMax; IL-15, IDD-1, IGIV-C, imatinib mesylate, ISIS-14803, ITF-1697, ivabradine hydrochloride; KRN-5500; L-365260, levetiracetam, levosimendan, licofelone, linezolid, LJP-1082, lopinavir lumiracoxib; MCC-478, melatonin, morphine hydrochloride, morphine-6-glucuronide, moxidectin; N-Acetylcarnosine, natalizumab, NM-702, NNC-05-1869, NSC-703940; Ocinaplon OM-89, omalizumab, omeprazole/ sodium bicarbonate, OPC-28326, ospemifene; PEG-filgrastim peginterferon alfa-2a, pegsunercept, pirfenidone, pralmorelin, pregabalin; Recombinant glucagon-like peptide-1 (7-36) amide, repifermin, RSD-1235; S-8184, selodenoson, sodium dichloroacetate, suberanilohydroxamic acid; TAS-102, terfenadine, teriparatide, tipranavir troxacitabine; Ximelagatran; YM-337. (c) 2003 Prous Science

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14735233&dopt=Abstract esomeprozole Nexium



esomeprazole, Nexium
Esomeprazole: A significant advance beyond omeprazole in the treatment of acid-related disease.

Rabasseda X, Cole P.

Medical Information Department, Prous Science, Barcelona, Spain. xrabasseda prous.com

The second-generation proton pump inhibitor (PPI) esomeprazole is a new chemical entity consisting of an optical isomer of omeprazole, which for many years has been acknowledged as the gold standard therapy in gastric acid-related disorders. Esomeprazole has demonstrated a unique pharmacokinetic profile and enhanced efficacy over omeprazole, with improved inter-patient pharmacokinetic consistency and a similar safety profile. Esomeprazole has been tested as a therapeutic agent in the management of erosive esophagitis, symptomatic gastroesophageal reflux disease (GERD) and, in combination with appropriate antibiotic therapy, for the eradication of the Helicobacter pylori bacterium and healing of H. pylori-associated duodenal ulcers. In clinical studies, esomeprazole has shown greater efficacy than omeprazole with a comparable low incidence of adverse events. (c) 2001 Prous Science. All rights reserved.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12738973&dopt=Abstract esomeprozole Nexium