Drugs online research references
sat.ap-hop-paris.fr
BACKGROUND: Helicobacter pylori resistance to clarithromycin is relatively frequent in France and is assumed to be the main cause of failure of the proton pump inhibitor-amoxicillin-clarithromycin (proton pump inhibitor-AC) therapy, which is the first-line regimen in France. AIM: To determine the respective effects of clarithromycin primary and secondary resistances on efficacy of the proton pump inhibitor-AC regimen and to determine whether failures are associated with persistence of the same strain or with emergence of a new one. METHODS: A total of 123 H. pylori-infected patients were treated for 7 days with omeprazole 20 mg b.d., amoxicillin 1 g b.d., and clarithromycin 500 mg b.d. Eradication was assessed by breath test in 102 patients. Minimal inhibitory concentrations of clarithromycin were determined by E-test. Strain genotyping was performed by random amplified polymorphic DNA. RESULTS: The pre-treatment and post-treatment prevalences of clarithromycin resistance were 19% (23 out of 123) and 69% (nine out of 13), respectively. The rates of eradication were 68% (69 out of 102), 79% (67 out of 85), and 12% (two out of 17) for all, susceptible and resistant strains, respectively. The post-treatment isolate was available for six patients with a susceptible pre-treatment isolate and a persistent infection. Resistance emerged in two patients and was associated with persistence of the pre-treatment strain in one and with selection of a new strain in the other. CONCLUSIONS: In our hospital, failures of the proton pump inhibitor-AC therapy are related to both clarithromycin primary and secondary resistances, but the emergence of secondary resistance does not explain all of the failures in the initial clarithromycin-susceptible group. In that group a new strain can emerge after failure.
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libero.it
Although the prevalence of reflux esophagitis is known to increase with age, data on the long-term outcome of esophagitis in elderly patients are scarce. We sought to evaluate the clinical outcome of elderly patients with esophagitis 6 months to 3 years after diagnosis and to identify specific prognostic indicators of a poor outcome. This was a long-term (6 months to 3 years) follow-up study. Patients older than 65 years of age diagnosed as having reflux esophagitis healed after acute treatment (2 to 4 months) were included in the study. Clinical examinations and upper gastrointestinal endoscopy were performed every 6 months for the first year and annually thereafter. After healing, no therapy was prescribed; in the event of symptom recurrence, a maintenance therapy consisting either of H2 blockers or proton pump inhibitors (PPI) was prescribed. At baseline and during follow-up, the following clinical parameters were recorded: gender, age, the presence of symptoms (heartburn, acid regurgitation, epigastric/chest pain), type and dose of the maintenance therapy, nonsteroidal antiinflammatory drug use; gastric Helicobacter pylori infection, diagnosis of hiatal hernia, and/or Barrett's esophagus. The chi-square test, the Kaplan-Meier test, and Cox's proportional hazards regression analysis were used for statistical analyses. Included in the final analysis were 138 patients (M/F, 81/57; mean age, 79.7 years; range, 66-97). The numbers of patients in need of maintenance therapy were 47 of 69 (68.1%) after 6 months, 29 of 58 (50%) after 12 months, 17 of 39 (43.6%) after 24 months, and 12 of 26 (46.1%) after 36 months of follow-up. A significantly higher esophagitis relapse rate was found in patients not treated compared with subjects who were in maintenance therapy: 59% versus 8.5% (P <.0001) at 6 months, 65.5% versus 20.7% at 12 months (P <.002), 63.6% versus 11.7% at 24 months (P =.003), and 57.1% versus 8.3% at 36 months (P =.02). No significant difference in relapse rate was found in patients treated with H2 blockers versus PPIs (21.7% versus 10%). The Cox model demonstrated that no maintenance treatment (P =.00001), the presence of typical symptoms (P =.00001), the presence of hiatal hernia (P =.03), and a high severity grade of esophagitis at baseline (P =.009) were risk factors for relapse of esophagitis. In elderly subjects, esophagitis relapse occurs in a high percentage of cases, particularly in patients not treated with antisecretory drugs. The presence of typical symptoms, hiatal hernia, and a severe grade of esophagitis are risk factors for relapse. The most effective measure for minimizing the occurrence of relapse is a maintenance therapy with antisecretory drugs.
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J Pharm Sci. 2002 Jul;91(7):1627-38.
Effect of omeprazole on oral and intravenous RS-methadone pharmacokinetics and pharmacodynamics in the rat.
Carlos MA, Du Souich P, Carlos R, Suarez E, Lukas JC, Calvo R.
Department of Pharmacology, School of Medicine, University of the Basque Country, Leioa, 48940 Spain.
The effect of omeprazole on oral and intravenous (iv) RS-methadone pharmacokinetics and pharmacodynamics was studied in awake, freely moving rats, which were divided in four groups: oral RS-methadone (3 mg/kg) was given (a) to a control group (CO(oral)) (n = 65) and (b) to an omeprazole pretreated group (OP(oral)) (n = 77), and iv RS-methadone (0.35 mg/kg) was administered (c) to a control group (CO(iv)) (n = 86) and (d) to an omeprazole pretreated group (OP(iv)) (n = 86). Omeprazole (2 mg/kg) was given iv 2 h before RS-methadone. Plasma concentrations of RS-methadone (Cp) were determined by high-performance liquid chromatography and analgesic response by tail flick for 0-180 min (oral) and 0-120 min (iv). RS-Methadone rate of absorption (mean +/- SE) was faster in OP(oral) (k(01) = 0.31 +/- 0.04 min(-1)) than in CO(oral) (k(01) = 0.05 +/- 0.007 min(-1)), consequently plasma peak concentrations (C(max)) were greater (197.41 +/- 33.70 ng/mL versus 83.54 +/- 7.97 ng/mL) and the time to reach C(max) (t(max)) was shorter (11.23 +/- 1.32 min versus 39.18 +/- 1.74 min). Mean area under the Cp-time curve (AUC(0-infinity)) and hence bioavailability of oral RS-methadone were increased by omeprazole without significant changes in the elimination. Omeprazole did not affect the pharmacokinetics of iv RS-methadone. The changes of the analgesic effect of RS-methadone as a function of time were similar in all four groups. In the CO(oral) group, Cp and analgesic effect were defined by the E(max) model. The relationship between Cp and drug effect in the OP(oral) group showed a counterclockwise hysteresis (k(e0) of 0.018 +/- 0.006 min(-1)). For the iv groups (CO(iv) and OP(iv)), the Cp-analgesic effect relationship was described by an E(max) sigmoid model and omeprazole did not affect the pharmacodynamic parameters. It is concluded that omeprazole causes an increase in the bioavailability of oral RS-methadone without modifying the analgesic response but affecting the Cp-effect relationship. Copyright 2002 Wiley-Liss Inc.
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