A clinical trial comparing pantoprazole and esomeprazole to explore the concept of achieving 'complete remission' in gastro-oesophageal reflux disease.

BACKGROUND AND AIM: The outcome of gastro-oesophageal reflux disease treatment is traditionally assessed by measuring endoscopically confirmed healing and symptom relief separately. Both terms together, indicating complete remission, are intuitively a more realistic clinical endpoint but are assessed less often. AIM: To explore this concept, we formally compared the efficacy of the proton pump inhibitors (PPIs) pantoprazole and esomeprazole using rates of complete remission judged against rates of healing and symptom relief separately. METHODS: Five hundred and eighty-two patients with erosive gastro-oesophageal reflux disease were randomized to treatment for 4, 8, or 12 weeks with either pantoprazole or esomeprazole 40 mg daily. Symptom relief was assessed with the validated ReQuesttrade mark-GI subscale. RESULTS: Approximately 75% of patients were free of symptoms or had no oesophageal lesions after 4 weeks' treatment, rising to about 93% and 96%, respectively, at 12 weeks. Complete remission rates were, however, lower at these time points; approximately 60% and about 90%, respectively. Both PPIs had similar efficacy. CONCLUSIONS: Endoscopically confirmed healing and symptom relief assessed separately over-estimated the benefits of both drugs. In contrast, complete remission indicates that patients may be treated inadequately when given the standard 4- to 8-week treatment. We suggest that complete remission is a more reliable and clinically relevant endpoint of treatment.

Esomeprazole MUPS 40 mg tablets and esomeprazole MUPS 40 mg tablets encapsulated in hard gelatine are bioequivalent.

OBJECTIVE: To investigate the bioequivalence of esomeprazole MUPS 40 mg tablets administered with and without a hard gelatine capsule. MATERIAL AND METHODS: Bioequivalence of the esomeprazole MUPS 40 mg tablet administered without (Reference) and with a hard gelatine capsule (Test) was evaluated using a randomized, two-period crossover study. In each study period 49 healthy male Caucasian subjects received a single oral dose of 40 mg esomeprazole. Blood samples were collected at specified time intervals, and serum was separated and analyzed for esomeprazole concentrations using a validated HPLC-MS method. The primary parameters were AUC (extent of absorption) and Cmax (rate of absorption). The time-to-peak plasma concentration, tmax, and the elimination half-life, t1/2, were determined as secondary characteristics. Point estimates and 90%-confidence intervals were obtained for the ratio of the population medians of Test and Reference, using a multiplicative model and a parametric analysis except in the case of tmax, where an additive model and a non-parametric analysis was used. Bioequivalence of Test and Reference was concluded if the 90%-confidence intervals were entirely within the predefined equivalence ranges. RESULTS: The AUC(0-infinity) and Cmax-ratios (Test/Reference) were 1.00 and 1.01, respectively. The 90%-confidence intervals for AUC(0-infinity) (0.94-1.06) and Cmax (0.93-1.09) of these ratios were within the predefined equivalence range of 0.80-1.25 and 0.75-1.33, respectively. The ratios and 90%-confidence intervals of the secondary characteristics t1/2 and tmax were also within the respective predefined equivalence ranges. Both esomeprazole formulations were well tolerated and safe. CONCLUSION: The encapsulation of esomeprazole MUPS 40 mg tablets does not influence the extent and rate of absorption assessed by using AUC(0-infinity) and Cmax. Thus, bioequivalence could be demonstrated.

Enantioselective degradation of alpha-hexachlorocyclohexane and cyclodiene insecticides in roe-deer liver samples from different regions of Germany.

Remarkably high concentrations of alpha-hexachlorocyclohexane (alpha-HCH), cis-heptachlorepoxide and oxychlordane were found in roe-deer liver samples both from the northern and southern German states Schleswig-Holstein and Baden-Württemberg, respectively. The data revealed no significant regional differences, but they showed some common characteristics: a preferential degradation of (+)-alpha-HCH, and a preferential enrichment of (+)-oxychlordane and of (+)-cis-heptachlorepoxide as determined by chiral capillary gas chromatography using modified cyclodextrin phases. Calculation of the spearman rank correlation coefficients rS supported the assumption that higher concentrations of alpha-HCH may result in a stronger decomposition of the (+)-enantiomer, while higher levels of cis-heptachlorepoxide and oxychlordane appear to lead to a faster decomposition of the respective (-)-enantiomer or a preferential formation of the respective (+)-enantiomer.

Enantioselective and nonenantioselective degradation of organic pollutants in the marine ecosystem.

Enantiomeric ratios of 11 chiral environmental pollutants determined in different compartments of the marine ecosystem by chiral capillary gas chromatography and chiral high-performance liquid chromatography allow discrimination between the following processes: enantioselective decomposition of both enantiomers with different velocities by marine microorganisms (alpha-HCH, beta-PCCH, gamma-PCCH); enantioselective decomposition of one enantiomer only by marine microorganisms (DCPP); enantioselective decomposition by enzymatic processes in marine biota (alpha-HCH, beta-PCCH, trans-chlordane, cis-chlordane, octachlordane MC4, octachlordane MC5, octachlordane MC7, oxychlordane, heptachlor epoxide); enantioselective active transport through the "blood-brain barrier" (alpha-HCH); nonenantioselective photochemical degradation (alpha-HCH, beta-PCCH).