esomeprazole, Nexium
Pharmacokinetic study of esomeprazole in patients with hepatic impairment.

Sjovall H, Bjornsson E, Holmberg J, Hasselgren G, Rohss K, Hassan-Alin M.

Sahlgrenska University Hospital, Goteborg, Sweden. henrik.sjovall medfak.gu.se

OBJECTIVE : To evaluate the pharmacokinetics and safety of esomeprazole (Nexium), the S-isomer of omeprazole, after repeated oral dosing in patients with hepatic impairment. DESIGN : Single-centre, open-label one-way study. METHODS : Twelve patients (aged 40-60 years) with mild to severe hepatic impairment received once-daily oral esomeprazole 40 mg for 5 days. Serial blood samples were drawn up to 24 h post-dose on day 5 to determine plasma levels of esomeprazole and its metabolites. Pharmacokinetic parameters were compared with an historical control group of 36 gastro-oesophageal reflux disease (GORD) patients (aged 29-58 years) with normal hepatic function. RESULTS : Esomeprazole was absorbed rapidly (mean maximum plasma concentration (Cmax) 6.1 micromol/l, mean time to Cmax (tmax) 1.9 h) and eliminated rapidly (mean plasma elimination half-life (t1/2) 2.1 h). Elimination of its pharmacologically inactive sulphone and hydroxy metabolites was more gradual. Patients with mild hepatic impairment had area under the plasma concentration-time curve during the dosage interval (AUCtau) and t1/2 values largely within the range of the control group. In patients with moderate hepatic impairment, t1/2 values were similar and AUCtau was slightly higher than in controls, whereas both parameters were increased in patients with severe hepatic impairment. The mean ratios of esomeprazole AUCtau, Cmax and t1/2 values in patients with and without hepatic impairment were 1.8, 1.3 and 1.3, respectively. CONCLUSIONS : The steady-state pharmacokinetics of esomeprazole were not altered substantially by mild or moderate hepatic impairment; however, plasma levels of esomeprazole were elevated in severe cases. Thus, dose adjustment appears unwarranted in mild or moderate hepatic impairment, but may be required in some severely impaired patients. Esomeprazole was tolerated well across the spectrum of hepatic impairment.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11984146&dopt=Abstract esomeprozole Nexium



esomeprazole, Nexium
Esomeprazole: a review of its use in the management of acid-related disorders in the US.

Scott LJ, Dunn CJ, Mallarkey G, Sharpe M.

Adis International Limited, 41 Centorian Drive, PB 65901, Mairangi Bay, Auckland 10, New Zealand. demail adis.co.nz

Esomeprazole, the S-isomer of omeprazole, is the first proton pump inhibitor to be developed as a single optical isomer. It provides better acid control than current racemic proton pump inhibitors and has a favourable pharmacokinetic profile relative to omeprazole. In large well designed 8-week trials in patients with erosive oesophagitis, esomeprazole recipients achieved significantly higher rates of endoscopically confirmed healed oesophagitis than those receiving omeprazole or lansoprazole. Esomeprazole was effective across all baseline grades of oesophagitis; notably, relative to lansoprazole, as the baseline severity of disease increased, the difference in rates of healed oesophagitis also increased in favour of esomeprazole. In two trials, 94% of patients receiving esomeprazole 40mg once daily achieved healed oesophagitis versus 84 to 87% of omeprazole recipients (20mg once daily). In a study in >5000 patients, respective healed oesophagitis rates with once-daily esomeprazole 40mg or lansoprazole 30mg were 92.6 and 88.8%. Resolution of heartburn was also significantly better with esomeprazole than with these racemic proton pump inhibitors. Long-term (up to 12 months) therapy with esomeprazole effectively maintained healed oesophagitis in these patients. Esomeprazole 20 or 40mg once daily for 4 weeks proved effective in patients with symptomatic gastro-oesophageal reflux disease (GORD) without oesophagitis. Eradicating Helicobacter pylori infection is considered pivotal to successfully managing duodenal ulcer disease. Ten days' triple therapy (esomeprazole 40mg once daily, plus twice-daily amoxicillin 1g and clarithromycin 500mg) eradicated H. pylori in 77 to 78% of patients (intention-to-treat) with endoscopically confirmed duodenal ulcer disease. Esomeprazole is generally well tolerated, both as monotherapy and in combination with antimicrobial agents. The tolerability profile is similar to that of other proton pump inhibitors. Few patients discontinued therapy because of treatment-emergent adverse events (<3% of patients) and very few (<1%) drug-related serious adverse events were reported. CONCLUSIONS: Esomeprazole is an effective and well tolerated treatment for managing GORD and for eradicating H. pylori infection in patients with duodenal ulcer disease. In 8-week double-blind trials, esomeprazole effectively healed oesophagitis and resolved symptoms in patients with endoscopically confirmed erosive oesophagitis. Notably, in large (n >1900 patients) double-blind trials, esomeprazole provided significantly better efficacy than omeprazole or lansoprazole in terms of both healing rates and resolution of symptoms. Long-term therapy with esomeprazole effectively maintained healed oesophagitis in these patients. Esomeprazole was also effective in patients with symptomatic GORD. Thus, esomeprazole has emerged as an effective option for first-line therapy in the management of acid-related disorders.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11985491&dopt=Abstract esomeprozole Nexium



esomeprazole, Nexium
Pharmacologic Management of Gastroesophageal Reflux Disease.

Ramakrishnan A, Katz PO.

Division of Gastroenterology and Hepatology, Graduate Hospital, Suite 501, Pepper Pavilion, 1800 Lombard Street, Philadelphia, PA 19146, USA.

The burden of gastroesophageal reflux disease (GERD) results from its widespread prevalence and the unfavorable impact of its symptoms on well-being and quality of life. Whereas abnormalities of the antireflux barrier (lower esophageal sphincter) are important in the pathophysiology of GERD, pharmacologic therapy for GERD is based on suppression of acid, which is responsible for the majority of the symptoms and for epithelial damage. Proton pump inhibitors (PPIs) are the agents of choice for achieving the goals of medical therapy in GERD, which include symptom relief, improvement in quality of life, and healing and prevention of mucosal injury. As a class, these drugs are extremely safe. The newest PPI, esomeprazole, brings a statistically significant increase in healing of mucosal injury and symptom relief in patients with erosive esophagitis, compared with omeprazole and lansoprazole. This article reviews the role of medical therapy in the short- and long-term management of symptomatic patients with or without erosive esophagitis, including extraesophageal presentations, GERD during pregnancy, and Barrett's esophagus. Management of refractory patients is addressed.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12095478&dopt=Abstract esomeprozole Nexium



esomeprazole, Nexium
[Proton pump inhibitors according to need. Always for heartburn]

[Article in German]

Labenz J.

Medizinische Klinik, Jung-Stilling-Krankenhaus, Siegen. J.Labenz t-online.de

Gastroesophageal reflux disease (GERD) is one of the most common medical problems. The large majority of patients so affected have no endoscopically evident disease, or only mild erosive reflux esophagitis. Since both forms of GERD are probably non-progressive, on-demand therapy aimed at adequately controlling symptoms is safe treatment. Proton pump inhibitors (PPI) are the drugs of choice for acute and long-term treatment. In 1999, the first study reporting on on-demand therapy with omeprazole was published. A clear superiority over placebo was found, as was also dependence of the effect on the dose. In the recent past, publications have reported on on-demand therapy with the s-isomer of omeprazole--esomeprazole. With success rates of around 90%, on-demand therapy has proven to be highly effective. On average, the patients take one 20 mg tablet of esomeprazole on every third to fourth day.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12119901&dopt=Abstract esomeprozole Nexium



esomeprazole, Nexium
Proton pump inhibitors: an update.

Vanderhoff BT, Tahboub RM.

Grant Medical Center, Columbus, Ohio, USA.

Since their introduction in the late 1980s, proton pump inhibitors have demonstrated gastric acid suppression superior to that of histamine H2-receptor blockers. Proton pump inhibitors have enabled improved treatment of various acid-peptic disorders, including gastroesophageal reflux disease, peptic ulcer disease, and nonsteroidal antiinflammatory drug-induced gastropathy. Proton pump inhibitors have minimal side effects and few significant drug interactions, and they are generally considered safe for long-term treatment. The proton pump inhibitors omeprazole, lansoprazole, rabeprazole, and the recently approved esomeprazole appear to have similar efficacy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12152963&dopt=Abstract esomeprozole Nexium