Drugs online research references
Crit Care Med. 2002 May;30(5):1118-22.
Omeprazole treatment diminishes intra- and extracellular neutrophil reactive oxygen production and bactericidal activity.
Zedtwitz-Liebenstein K, Wenisch C, Patruta S, Parschalk B, Daxbock F, Graninger W.
Division of Infectious Diseases, Department of Internal Medicine I, University Hospital, Vienna, Austria.
OBJECTIVE: Neutrophils play a crucial role in host defense against infectious disease. The objective was to analyze the effect of omeprazole treatment on indexes of neutrophil function in healthy subjects. DESIGN: Open. SETTING: University hospital. SUBJECTS: Ten healthy subjects. INTERVENTION: Analysis of blood samples before and after omeprazole administration. MEASUREMENTS AND MAIN RESULTS: Neutrophil Escherichia coli phagocytosis was assessed by microscopy and flow cytometry. Intracellular production of reactive oxygen intermediates was measured by flow cytometry. Extracellular reactive oxygen intermediate production was assessed with a cytochrome c reduction assay. Neutrophil bactericidal capacity and intracellular concentrations of Ca2+ were determined by fluorometry. Four hours after a single 40-mg dose of omeprazole, intra- and extracellular reactive oxygen intermediate production by neutrophils was significantly reduced compared with pretreatment values: -30% (24% to 42%) (median and range) and -22% (21% to 68%; p <.05 for both). The intracellular Ca2+ concentrations in resting neutrophils were significantly increased (+33%, 21% to 39%, compared with pretreatment concentrations, p <.001) and neutrophilic bactericidal activity was decreased (-30%, 19% to 47%, compared with pretreatment concentrations, p <.0001). Intracellular Ca2+ concentrations correlated with intracellular reactive oxygen intermediate production and neutrophilic bactericidal capacity (r =.730 and r =.618, p <.05 for both, respectively). In contrast, phagocytosis rates were not impaired by omeprazole. CONCLUSIONS: Our results imply that omeprazole impairs production of reactive oxygen intermediates by neutrophils. Whether specific impairments of neutrophil host defenses occur in vivo remains uncertain. Reduced bactericidal activity is associated with an increase of intracellular Ca2+ concentrations in resting neutrophils.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12006811&dopt=Abstract
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Clin Pharmacol Ther. 2002 May;71(5):359-67.
Pharmacokinetic-pharmacodynamic study of oral lansoprazole in children.
Tran A, Rey E, Pons G, Pariente-Khayat A, D'Athis P, Sallerin V, Dupont C.
Pharmacologie Perinatale et Pediatrique, Gastroenterologie Pediatrique, Universite Rene Descartes, Hopital Saint-Vincent de Paul, 82 Avenue Denfert-Rochereau, Assistance Publique-Hopitaux de Paris, 75674 Paris, France.
OBJECTIVE: We investigated the pharmacokinetics, pharmacodynamics, and tolerability of lansoprazole in children after single and multiple administrations. METHODS: Forty children (age range, 18 days-14 years) with gastric acid-related disorders entered an open study and received lansoprazole in a single dose of 17 mg. m(-2) (group A) or in multiple doses (17 mg. m(-2) per day) for 7 to 14 days (group B). Lansoprazole plasma concentrations were measured by HPLC. A 24-hour intragastric pH monitoring assessed the antisecretory effect. RESULTS: In group A, maximal concentration (C(max)) was 1023 +/- 775 (mg. L(-1))/(17 mg. m(-2)), time to reach C(max) was 1.8 +/- 0.8 hours, elimination half-life was 1.5 +/- 2.0 hours, area under the concentration-time curve from time zero to infinity [AUC(0-infinity)] was 3503 +/- 6025 (mg. L(-1). h)/(17 mg. m(-2)), apparent plasma clearance was 0.57 +/- 0.47 L. h(-1). kg(-1), and apparent volume of distribution was 0.61 +/- 0.36 L. kg(-1). In group B, C(max) was 750 +/- 511 (mg. L(-1))/(17 mg. m(-2)), time to reach C(max) was 1.8 +/- 1.1 hours, elimination half-life was 1.2 +/- 1.1 hours, AUC(0-infinity) was 2351 +/- 3691 (mg. L(-1). h)/(17 mg. m(-2)), apparent plasma clearance was 0.71 +/- 0.50 L. h(-1). kg(-1), and apparent volume of distribution was 0.9 +/- 0.7 L. kg(-1). No influence of age was shown on pharmacokinetic parameters in both groups. However, data suggested that elimination was reduced in neonates and higher in infants than in adults. The values for 24-hour percentage of time at gastric pH <4 and pH <3 were 61% +/- 21% and 51% +/- 21% (group A) and 47% +/- 24% and 37% +/- 21% (group B), respectively. In both groups the antisecretory effect decreased with age, and in group A it was positively correlated to C(max) and AUC(0-infinity). The mean gastrin serum concentration significantly increased (+31%) after 12.6 +/- 1.5 days of treatment. CONCLUSIONS: Lansoprazole was well tolerated in children. After a single oral dose of 30 mg per 1.73 m(2), there was a trend for the elimination to be higher in infants than in adults and the antisecretory effect appeared to be higher in infants younger than 6 months than in older children and adults.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12011821&dopt=Abstract
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Acta Gastroenterol Belg. 2002 Jan-Mar;65(1):17-23.
Gastric MALT-lymphoma, gastrin and cyclooxygenases.
Konturek PC, Konturek SJ, Pierzchalski P, Starzynska T, Marlicz K, Hartwich A, Zuchowicz M, Darasz Z, Papiez D, Hahn EG.
Department of Physiology, University College of Medicine, 16 Grzegorzecka str, 31-531 Krakow, Poland.
Malt-lymphoma, gastrin and COX-2 interaction. Low grade, mucosal associated lymphoid tissue (MALT)-lymphoma is an unique among gastric malignancies where causal involvement of Helicobacter pylori (H. pylori) infection has been proposed based on complete regression of the tumor following the eradication therapy. In this report ten primary, low-grade MALT-lymphomas have been examined before and 6 months after one week of successful eradication therapy (clarithromycin + amoxicillin + omeprazole). Gastric biopsy samples from tumor and intact antrum and corpus mucosa were obtained during endoscopy before and after eradication for assessment of expression of gastrin and gastrin receptor (CCKB-R) as well as cyclooxygenase (COX)-1 and COX-2 using RT-PCR. The gastric lumen and serum gastrin and mucosal and tumor tissue PGE2 biosynthesis were determined by RIA before and after H. pylori eradication. Eradication of H. pylori resulted in complete endoscopic and histological remission of MALT-lymphoma in 9 out of 10 patients as assessed 6 months after this eradication. Before eradication, the mRNA expression for gastrin and CCKB-R as well as mRNA expression for COX-1 and COX-2 were observed in tumor tissue and infected mucosa, while corpus mucosa expressed only CCKB-R and antrum mucosa only gastrin. Six months upon the eradication when MALT-lymphoma completely regressed both endoscopically and histologically in 9 of 10 tested subjects, the expression of gastrin and COX-2 disappeared from the former area of MALT-lymphoma tumor. Gastrin mRNA remained detectable only in antrum mucosa, CCKB-R mRNA in corpus mucosa and COX-1 mRNA both in antrum and corpus mucosa. Gastric luminal and serum gastrin levels and gastric mucosa and tumor PGE2, which were greatly elevated before eradication, became normalized after this procedure. This study demonstrates that low-grade MALT-lymphoma is linked to H. pylori infection which may promote the expression and excessive release of gastrin and COX-2 expression that could be involved in the pathogenesis of MALT-lymphoma.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12014312&dopt=Abstract
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