Background: Rabeprazole sodium is the most recent member of a class of substituted benzimidazole molecules known as proton pump inhibitors. Other proton pump inhibitors have been shown to be effective in healing oesophagitis. Methods: In this randomised, double‐blind, multicentre study, conducted at 27 European sites, the efficacy and safety of rabeprazole and omeprazole were compared in patients with erosive or ulcerative gastro‐oesophageal reflux disease (GERD).100 patients received rabeprazole 20 mg, and 102 patients omeprazole 20 mg once daily for 4 or 8 weeks, with healing monitored by endoscopy. Results: Overall GERD healing rates observed and evaluated at weeks 4 and 8 were equivalent. Four‐week healing rates for rabeprazole and omeprazole were 81%–81% and 92%–94% for 8‐week healing. Rabeprazole‐treated patients had similar relief of the frequency and intensity of heartburn to those treated with omeprazole. Both drugs were well tolerated over the 8‐week treatment period. Mean changes in fasting serum gastrin were comparable. No significant differences in laboratory parameters were seen. Biopsies for argyrophil ECL cell histology at the end‐point revealed a similar distributions of hyperplasia grades to those at baseline in both groups. Biopsies of body and antral mucosa for other parameters were similar between treatments for Helicobacter pylori colonization, presence or degree of inflammation, atrophy or intestinal metaplasia at the end‐point. Conclusion: In this study, GERD healing rates following rabeprazole 20 mg once daily were equivalent to those obtained with omeprazole 20 mg once daily. Both treatments resulted in a comparable relief of the frequency and intensity of heartburn associated with this disease, and both were well tolerated.

Summary. PEGylation is the technology involving the covalent attachment of polyethylene glycol (PEG) to a protein-, peptide-or small-molecule drug to improve their pharmacokinetic, pharmacodynamic and immunological profiles, and thus, enhance the therapeutic effect. Today, PEGylation of proteins is a well-established technology and is being used in the treatment of a variety of clinical disorders. Several PEGylated coagulation proteins for haemophilia A and B are under development with the goal of prolonging the circulation half-life of factor VIII (FVIII) or factor IX. The prolongation of half-life, resulting in less frequent injections can provide significant benefits in improving the quality of life of subjects with haemophilia and improvement in adherence to treatment. A review of published literature on PEGylated therapeutic products currently approved for human use and a discussion of a PEGylated recombinant FVIII molecule (BAY 94-9027, Bayer HealthCare, Berkeley, CA, USA) currently being investigated in the pivotal clinical trial prior to registration is provided. Available safety information of PEGylated proteins containing high molecular weight PEG does not indicate any safety concerns to date, following long-term (chronic) use in animal models or patients. Chronic use of currently available PEGylated products has been shown to be safe, paving the way for chronic use of PEGylated coagulation products in persons with haemophilia.

There is conflicting evidence in the literature on whether individuals with haemophilia in the USA have greater, reduced, or similar risks for cardiovascular disease as the general population. This study evaluated the prevalence of cardiovascular comorbidities among USA males with haemophilia A, relative to an unaffected general male population with similar characteristics. Males with haemophilia A and continuous insurance coverage were identified by ICD-9-CM code 286.0 (1 January 2007-31 December 2009) using the MarketScan Commercial and Medicare Research Databases. Individuals with haemophilia A were exact matched 1:3 with males without a diagnosis of haemophilia A. The prevalence of cardiovascular comorbidities identified by ICD-9-CM code was determined for matched cohorts. Of the study population, 2506 were grouped in the haemophilia A cohort and 7518 in the general cohort. Proportions of individuals with haemorrhagic stroke (2.0% vs. 0.5%, P < 0.001), ischemic stroke (4.7% vs. 2.7%, P < 0.001), coronary artery disease (10.7% vs. 5.8%, P < 0.001), myocardial infarction (0.8% vs. 0.3%, P = 0.003), hypertension (22.6% vs. 15.5%, P < 0.001), hyperlipidaemia (15.9% vs. 11.9%, P < 0.001), arterial thrombosis (12.1% vs. 5.9%, P < 0.001), and venous thrombosis (4.4% vs. 1.1%, P < 0.001) were significantly greater for the haemophilia A cohort. Results were consistent across most age groups, and comorbidities appeared at an earlier age in those with haemophilia A than in the general population. Among the USA haemophilia A population cardiovascular comorbidities are more prevalent and they appear earlier in life in comparison to the general male population, suggesting the need for earlier, enhanced screening for age-related comorbidities in the haemophilia community.

Patients with acid-related diseases often need to take multiple medications. Treatment of Helicobacter pylori infection often includes either a histamine type 2 (H2)-receptor antagonist or a proton pump (H+,K(+)-ATPase) inhibitor (proton pump inhibitor), administered in conjunction with one or more antimicrobials. Also, treatment for acid-related diseases often requires extended therapy during which many concomitant medications may be administered for concurrent disease states. Polypharmacy may be the result, particularly in elderly patients, who are at increased risk for both acid-related and many other diseases. Thus, it is important to understand the potential for clinically significant drug-drug interactions in this setting. H2-receptor antagonists and proton pump inhibitors can influence the pharmacokinetic profiles of other commonly administered medications by elevating intragastric pH, which can alter drug absorption, and by interacting with the cytochrome P (CYP) 450 enzyme system, which can affect drug metabolism and clearance. Such interactions are particularly important when they affect the pharmacokinetics of drugs with narrow therapeutic ranges (e.g. warfarin, digoxin). In these cases, drug-drug interactions can result in significant toxicity and even death. There are marked differences among H2-receptor antagonists and proton pump inhibitors in their potential for such interactions. The oldest drugs in each class, cimetidine and omeprazole, respectively, have the greatest potential to alter CYP activity and change the pharmacokinetics of other drugs. The most recently developed H2-receptor antagonist, famotidine, and the newer proton pump inhibitors, rabeprazole and pantoprazole, are much less likely to induce or inhibit CYP and thereby change the metabolism of other medications. These differences are important when choosing medications for the safe treatment of patients with acid-related diseases.

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