Prevacid
Pharmacokinetic differences between lansoprazole enantiomers in rats.

Arimori K, Yasuda K, Katsuki H, Nakano M.

Department of Pharmacy, Kumamoto University Hospital, Japan.

Because limited information is available about potential differences between the pharmacokinetics and pharmacodynamics of the enantiomers of lansoprazole, the enantioselective pharmacokinetics of the compound have been investigated in rats. There was a noticeable difference between the serum levels of the enantiomers of lansoprazole and of their metabolites, 5-hydroxylansoprazole enantiomers, after oral administration of the racemate (50 mg kg(-1)) to rats. Cmax (maximum serum concentration) and AUC (area under the serum concentration-time curve) for (+)-lansoprazole were 5-6 times greater than those for (-)-lansoprazole, whereas for (+)-5-hydroxylansoprazole both values were significantly smaller than those for the (-) enantiomer. CLtot/F values (where CLtot is total clearance and F is the fraction of the dose absorbed) for (+)-lansoprazole were significantly smaller than those for the (-) enantiomer. There was no significant difference between the absorption rate constants of the lansoprazole enantiomers in the in-situ absorption study. The in-vitro protein-binding study showed that binding of (+)-lansoprazole to rat serum proteins was significantly greater than for the (-) enantiomer. The in-vitro metabolic study showed that the mean metabolic ratio (45.9%) for (-)-lansoprazole was significantly greater than that (19.8%) for the (+) enantiomer in rat liver microsomes at 5.6 microM lansoprazole. These results show that the enantioselective disposition of lansoprazole could be a consequence of the enantioselectivity of plasma-protein binding and the hepatic metabolism of the enantiomers.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9877309&dopt=Abstract lansoprazole Prevacid



Prevacid
Bactericidal activity of lansoprazole and three macrolides against Helicobacter pylori strains tested by the time-kill kinetic method.

Fera MT, Carbone M, De Sarro A, Blandino G, Riggio G, Cusumano V, De Sarro GB, Ciliberti FA.

Istituto di Microbiologia, Facolta di Medicina e Chirurgia, Universita di Messina, Italy. Teti eniware.it

The bactericidal activities of macrolides (clarithromycin, roxithromycin and azithromicyn) and lansoprazole, alone and in combination, against Helicobacter pylori strains were evaluated. It was found that the association of lansoprazole and clarithromycin resulted in a marked synergism, while the combination of roxithromycin or azithromycin with lansoprazole had synergistic and additive effects.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9916902&dopt=Abstract lansoprazole Prevacid



Prevacid
Effect of omeprazole, lansoprazole, and ranitidine on the DNA synthesis of mononuclear cells.

Peddicord TE, Olsen KM, Collier DS.

Department of Pharmacy Practice, University of Nebraska Medical Center, Omaha 68198-6045, USA.

OBJECTIVE: To examine and compare the effects of omeprazole, lansoprazole, and ranitidine on the DNA synthesis of peripheral blood mononuclear cells. DESIGN: Ex vivo laboratory study. SETTING: Clinical research laboratory of an academic medical center. SUBJECTS: Healthy volunteers. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Venous blood was collected from normal subjects and peripheral blood mononuclear cells (PBMCs) were isolated using centrifugation techniques over a Ficoll-Hypaque density gradient. PBMCs were added to 12-well culture plates in four groups of media: a) control; b) control plus lansoprazole (25 microg/mL); c) control plus omeprazole (0.35 microg/mL); and d) control plus ranitidine (50 microg/mL). PBMCs were exposed to the drug for 96 hrs, with addition of phytohemagglutinin (2.5 microg/ mL) for the last 48 hrs, and 3H-thymidine (1 microCi) during the final 6 hrs. PBMCs were filtered onto glass-fiber filter paper and the radioactivity was determined by scintillation counting. Since radioactivity is measured only in those cells undergoing DNA synthesis or cell division, results are expressed as quantification of 3H-thymidine uptake. Median disintegrations per min (DPM)/number of PBMCs per well+/-SEM are reported: control 68.3+/-37.8; ranitidine 38.4 +/-94.2; lansoprazole 14.6+/-84.4; and omeprazole 15.1+/-48.9. There was a significant difference between lansoprazole vs. ranitidine (p< .01), and omeprazole vs. ranitidine (p< .05), and no significant difference between lansoprazole and omeprazole. CONCLUSIONS: This is the first study to compare the potential immunomodulating effects of these commonly used agents. Ranitidine caused increased DNA synthesis in PBMCs when compared with lansoprazole and omeprazole. This phenomenon may be an important, often disregarded, effect of histamine-2-receptor antagonists when used in postsurgical or trauma patients who have T-lymphocyte-mediated immune suppression.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9934899&dopt=Abstract lansoprazole Prevacid



Prevacid
[Clinical effect of proton pump inhibitors on reflux esophagitis]

[Article in Japanese]

Sekiguchi T, Horikoshi T, Nishioka T, Kusano M.

First Department of Internal Medicine, Gunma University School of Medicine.

The clinical efficacy of proton pump inhibitors (PPI, omeprazole 20 mg or lansoprazole 30 mg), once daily, after breakfast, was studied in patients with erosive/ulcerative reflux esophagitis. The following results were obtained. 1) Twenty-four hour esophageal pH monitoring was performed before treatment and on 7th day of PPI medications. Omeprazole reduced the percent time pH less than 4 from 29.1 to 1.2 and lansoprazole from 68.0 to 2.4. 2) The cumulative disappearance rate of overall symptom was 52% after 1 week and 62% after 2 weeks with omeprazole these were 66% and 91%, and with lansoprazole respectively 3) The endoscopic healing rate was 63% was after 2 weeks and 76% after 4 weeks with omeprazole medication, and 76% and 97% respectively with lansoprazole. These results indicate that PPI medication inhibits the acid reflux almost completely and is a more useful therapeutic agent for GERD than H2-antagonists.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1311780&dopt=Abstract lansoprazole Prevacid



Prevacid
[Proton pump inhibitors in the treatment of peptic ulcers resistant to H2-receptor antagonists]

[Article in Japanese]

Asaka M, Kato M, Sato Y, Miyazaki T.

Third Department of Internal Medicine, School of Medicine, Hokkaido University.

The aim of this study is to evaluate the therapeutic effect of proton pump inhibitors on peptic ulcers resistant to H2-receptor antagonists. Patients with ulcers resistant to at least 3 months treatment with standard or greater doses of H2-receptor antagonists were treated with 20 mg of omeprazole or 30 mg of lansoprazole, once daily, for 2 to 8 weeks. Endoscopy was performed every 2 weeks to confirm ulcer healing. Eleven of 28 (39%) gastric ulcers healed within 4 weeks and 20 (71%) within 8 weeks with omeprazole. Eight of 19 (42%) gastric ulcers healed within 4 weeks and 14 (74%) within 8 weeks with lansoprazole. All of the duodenal ulcer healed within 6 weeks with omeprazole or lansoprazole. No adverse effects were observed in this study. These results suggest that proton pump inhibitors are highly effective in the treatment of peptic ulcer resistant to H2-receptor antagonists.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1347322&dopt=Abstract lansoprazole Prevacid