Prevacid
An evaluation of the CYP1A induction potential of pantoprazole in primary rat hepatocytes: a comparison with other proton pump inhibitors.

Masubuchi N, Okazaki O.

Drug Metabolism and Analytical Chemistry Research Laboratory, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.

The ability of pantoprazole to affect the induction of cytochrome P450 (CYP) 1A subfamily was evaluated and compared with two other proton pump inhibitors, omeprazole and lansoprazole, in primary cultured hepatocytes from female Sprague-Dawley rats. The hepatocytes were cultured for 2 days, followed by treatment for 2 days with the proton pump inhibitors at 2, 5 and 10 microM, concentrations that are similar to plasma concentrations found in rats in vivo. The CYP1A inducer 3-methylcholanthrene (at 1 microM) was also evaluated as a positive control. Induction potentials of these chemicals for CYP1A were determined by 7-ethoxyresorufin O-deethylase activity and isozyme contents. The results showed that for CYP1A induction, the rank ordering in induction potential was consistently lansoprazole > omeprazole > pantoprazole. The results are consistent with the existing rat in vivo data, i.e. pantoprazole has lower CYP1A induction potential than omeprazole and lansoprazole.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9402950&dopt=Abstract lansoprazole Prevacid



Prevacid
Effects of proton pump inhibitors on thyroid hormone metabolism in rats: a comparison of UDP-glucuronyltransferase induction.

Masubuchi N, Hakusui H, Okazaki O.

Drug Metabolism and Analytical Chemistry Research Laboratory, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan. XLB05644 niftyserve.or.jp

The effects of proton pump inhibitors on thyroid hormone metabolism in rats were examined. Pantoprazole, omeprazole, and lansoprazole were administered repeatedly to female SD rats at doses of 5, 50, and 300 mg/kg/day for 1 week, and changes in UDP-glucuronyltransferase activities were examined. Increases in o-aminophenol UDP-glucuronyltransferase activity, which was measured as that responsible for the glucuronidation of thyroxine, were evident following 7-day high-dose administration of all the proton pump inhibitors tested. Of the three proton pump inhibitors investigated, o-aminophenol UDP-glucuronyltransferase activity was greatest following the high-dose administration of omeprazole. Androsterone UDP-glucuronyltransferase activity in rats treated with the proton pump inhibitors increased significantly, but these increases were smaller than those of o-aminophenol UDP-glucuronyltransferase. Pantoprazole and omeprazole treatment did not affect plasma T4 or T3 significantly, whereas lansoprazole treatment produced marked reductions in plasma T4 but did not affect plasma T3 significantly. After administration of 125I-labeled thyroid hormone to rats treated with the proton pump inhibitors, biliary excretion of radioactivity increased significantly in omeprazole- and lansoprazole-treated rats; these increases were attributed to induction of liver thyroxine UDP-glucuronyltransferase activities. The order of biliary excretion of radioactivity, as well as the o-aminophenol UDP-glucuronyltransferase activity, in the treated animals was: omeprazole > lansoprazole > pantoprazole. Therefore, repeated administration of the proton pump inhibitors increased thyroxine-metabolizing activity via induction of UDP-glucuronyltransferase, and this induction by pantoprazole was less pronounced than that by omeprazole or lansoprazole.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9416973&dopt=Abstract lansoprazole Prevacid



Prevacid
Effects of enprostil on gastric endocrine secretion during chronic administration of lansoprazole.

Omura N, Kashiwagi H, Aoki T, Omura K, Fukuchi Y.

Department of Surgery (II), Jikei University School of Medicine, Tokyo, Japan.

We investigated changes in the secretory kinetics of gastric endocrine cells related to the administration of lansoprazole, and the effects of enprostil on these altered kinetics. Male Wistar-derived 8-week-old rats were allotted to a control group, a lansoprazole administration group, an enprostil administration group, and a lansoprazole + enprostil administration group. Lansoprazole (30 mg/kg once a day for 4 weeks) and enprostil (10 micrograms/kg twice a day for 4 weeks) were administered into the gastric lumen with a gastric tube. At this time, blood was collected and immunohistological staining of gastric endocrine cells was conducted to investigate the secretory kinetics. Lansoprazole administration induced hypergastrinemia, increase of gastrin cells, and increase of enterochromaffin-like cells. Enprostil administration induced increase of somatostatin cells. The group administered lansoprazole + enprostil exhibited significant decreases in serum gastrin level, total gastrin cell count, and total enterochromaffin-like cell count, compared with the group administered lansoprazole alone. These findings suggest that enprostil may ameliorate the alteration in gastric endocrine secretion produced by the chronic administration of lansoprazole.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9430011&dopt=Abstract lansoprazole Prevacid



Prevacid
Lansoprazole and ethanol metabolism: comparison with omeprazole and cimetidine.

Battiston L, Tulissi P, Moretti M, Pozzato G.

Institute of Clinical Medicine, University of Trieste, Italy.

Since some antisecretory drugs such as cimetidine and ranitidine, interfere with ethanol metabolism by inhibition of hepatic and/or gastric alcohol dehydrogenase, we investigated the effect of lansoprazole, a new protonic pump inhibitor, on gastric and hepatic alcohol dehydrogenase activity. We also compared the lansoprazole effect with that of omeprazole and cimetidine, respectively. Ethanol blood concentration after oral intake or intravenous administration of ethanol was estimated either in normal male human volunteers or in male rats before and after one week pretreatment with lansoprazole, omeprazole and cimetidine. Furthermore, the in vitro effect of these drugs was studied on both human and rat gastric and hepatic alcohol dehydrogenases. Finally, we measured the effect of the treatment on the reduced hepatic glutathione to test the effects of the drugs on first-pass metabolism of ethanol. The results reported in this paper indicate that lansoprazole, as well as omeprazole, does not affect ethanol metabolism, and that protonic pump inhibitors seem to be safer than imidazole-derived drugs in subjects unable to reduce ethanol intake during conditions requiring acid secretion inhibition.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9444664&dopt=Abstract lansoprazole Prevacid



Prevacid
Helicobacter pylori gastritis and epithelial cell proliferation in patients with reflux oesophagitis after treatment with lansoprazole.

Berstad AE, Hatlebakk JG, Maartmann-Moe H, Berstad A, Brandtzaeg P.

Laboratory for Immunohistochemistry and Immunopathology (LIIPAT), University of Oslo, National Hospital, Rikshospitalet, Norway.

BACKGROUND: Helicobacter pylori gastritis may spread proximally in the stomach during profound acid inhibition. AIMS: To examine histological gastric body changes and epithelial cell proliferation before and after treatment with lansoprazole. PATIENTS AND METHODS: Patients diagnosed as having reflux oesophagitis grade 1 or 2 were enrolled and treated for 12 weeks with lansoprazole (30 mg every morning). After 12 weeks, 103 of the 118 patients appeared endoscopically healed and were asymptomatic; they then received maintenance treatment with 15 or 30 mg lansoprazole daily. Biopsy specimens obtained from similar sites before and after treatment, were available from 90 patients after a median of 64 weeks (range 15-73 weeks). Epithelial cell proliferation was determined by the number of Ki-67 antigen positive cells per gland. RESULTS: Of these 90 patients, 44 (49%) were found to be infected with H pylori. Their median inflammation score had increased from grade 1 before to grade 2 after treatment (p < 0.0001). Initially, the number of Ki-67 antigen positive cells per gland was significantly higher in the H pylori infected than in the uninfected group and increased further after treatment (p < 0.0001). In uninfected patients, no significant change in inflammation or proliferation occurred during treatment. CONCLUSIONS: A marked increase in body gastritis was observed in H pylori infected individuals during long term treatment with the proton pump inhibitor lansoprazole. Epithelial cell proliferation and atrophy also increased in infected but not in uninfected patients.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9462205&dopt=Abstract lansoprazole Prevacid