Prevacid
Lansoprazole and omeprazole have similar effects on plasma gastrin levels, enterochromaffin-like cells, gastrin cells and somatostatin cells in the rat stomach.

Lee H, Hakanson R, Karlsson A, Mattsson H, Sundler F.

Gastrointestinal Pharmacology, Preclinical Research and Development, Astra Hassle AB, Molndal, Sweden.

This study compares the effects of lansoprazole and omeprazole on the activation and proliferation of enterochromaffin-like (ECL) cells in the rat stomach. Lansoprazole was given orally once daily for 10 weeks in two doses, 135 and 200 mumol/kg. Omeprazole was given by the same regimen in a dose of 400 mumol/kg, which is equipotent in terms of acid inhibition to the higher lansoprazole dose. Lansoprazole (both doses) as well as omeprazole raised the plasma gastrin levels about 11-fold 2 h after dosing and 8-to 10-fold 24 h after dosing, reflecting complete (2 h) and 70-80% (24 h) reductions of gastric acid secretion. Administration of either drug for 10 weeks increased the weight of the stomach and the oxyntic mucosa. The oxyntic mucosal histidine decarboxylase activity, histamine concentration and ECL cell density were increased to the same extent in the rats given either of the two lansoprazole doses or omeprazole. The numbers of antral gastrin cells were doubled and the numbers of antral somatostatin cells half that in the controls. These results show that long-standing lansoprazole-evoked hypergastrinemia affects the ECL cell similarly to omeprazole, ranitidine and other acid secretion inhibitors.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1355746&dopt=Abstract lansoprazole Prevacid



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Determination of lansoprazole and its metabolites in plasma by high-performance liquid chromatography using a loop column.

Landes BD, Miscoria G, Flouvat B.

Laboratoire de Toxicologie et de Pharmacocinetique, Hopital Ambroise Pare, Boulogne Billancourt, France.

A high-performance liquid chromatographic method for the simultaneous determination of lansoprazole, a new proton pump inhibitor, and its metabolites in human plasma is described. Lansoprazole, its metabolites and an internal standard were extracted with tert.-butyl methyl ether. Samples were injected using an automatic injector via a loop column, and separation was obtained using a reversed-phase column under isocratic conditions. The absorbance was monitored at 285 and 303 nm. The quantification limit was 2 ng/ml for lansoprazole and 3 or 5 ng/ml for the metabolites. No endogenous compounds were found to interfere. The mean overall recovery was between 75 and 95% for lansoprazole and its metabolites. This method is suitable for pharmacokinetic studies.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1400730&dopt=Abstract lansoprazole Prevacid



Prevacid
The H+, K(+)-ATPase inhibitor pantoprazole (BY1023/SK&F96022) interacts less with cytochrome P450 than omeprazole and lansoprazole.

Simon WA, Budingen C, Fahr S, Kinder B, Koske M.

Byk Gulden Pharmazeutika, Konstanz, Germany.

The gastric acid antisecretory compound omeprazole (5-methoxy-2-((4-methoxy- 3,5-dimethyl-2-pyridinylmethyl)-sulphinyl)-1H-benzimidazole), a member of the new class of H+, K(+)-ATPase inhibitors, is known to interact with the metabolism of other drugs in vitro and in vivo. In this study, two other substituted benzimidazoles, pantoprazole (5-difluoromethoxy-2-((3,4-di-methoxy-2-pyridinylmethyl)-s ulp hinyl)-1H- benzimidazole) and lansoprazole (2-((3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinylmethyl)- sulphinyl)-1H-benzimidazole) are compared for their ability to inhibit cytochrome P450 dependent biotransformation in vitro with regard to three representative reactions: O-dealkylation of 7-ethoxycoumarin (EC), N-demethylation of ethylmorphine (EM) and hydroxylation of lonazolac (Lona). These reactions can be seen in microsomes from phenobarbital pretreated rats representing the cytochrome P450IIB1 subfamily. As shown in presence of known inhibitors of cytochrome P450, e.g. SK&F 525A, metyrapone, chlorpromazine and nitrendipine, different enzymes seem to be responsible for these three indicator reactions of the cytochrome P450IIB1 complex. These reactions are inhibited to a different extent by the three H+, K(+)-ATPase inhibitors. Pantoprazole shows the lowest inhibitory activity versus the three reactions (Ki, mumol/L): EC, 138; EM, 104; Lona, 128. A greater effect is observed with omeprazole: EC, 38; EM, 68; Lona, 20. Lansoprazole exceeds omeprazole in inhibiting the three cytochrome P450 dependent enzymes: EC, 17; EM, 34; Lona, 8. In microsomes from untreated rats with the predominant cytochrome P450IIA1 subfamily as well as in microsomes from isopropanol treated rats (induction of cytochrome P450IIE1) which catalyse only lonazolac hydroxylation to a detectable amount, the latter reaction was inhibited by pantoprazole with a somewhat lower Ki of 77 whereas the values for omeprazole and lansoprazole remained unchanged in comparison to those found in microsomes from phenobarbital pretreated rats. The biotransformation rate of the substituted benzimidazoles themselves in microsomes from control and induced rats is lowest for pantoprazole followed by lansoprazole and omeprazole.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1650212&dopt=Abstract lansoprazole Prevacid



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In vivo cytochrome P 450 interactions of the newly developed H+/K(+)-ATPase inhibitor pantoprazole (BY 1023/SK&F 96022) compared to other antiulcer drugs.

Hanauer G, Graf U, Meissner T.

Department of Pharmacology, Byk Gulden Pharmaceuticals, Konstanz, Germany.

Almost 10% of adverse drug reactions observed in clinical patients are due to interactions of two or more therapeutic agents (18). The aim of the present study was to investigate in vivo interactions of the H2-blocker cimetidine and three newly developed H+/K(+)-ATPase inhibitors, omeprazole, lansoprazole and pantoprazole (BY 1023/SK&F 96022) with cytochrome P 450 in rats. Because diazepam is a drug used very often as comedication in ulcer patients, the duration of the effects of diazepam on muscle coordination were used to evaluate the drug interactions on metabolic enzymes. The present data indicate a clear rank order of the antiulcer drugs' potency for interaction with diazepam: 1) lansoprazole with a 50% prolongation of diazepam effect at 170 mumol/kg, 2) cimetidine and omeprazole at 281 and 288 mumol/kg, respectively and 3) pantoprazole at greater than 1000 mumol/kg. Because the three H+/K(+)-ATPase inhibitors are approximately equipotent with respect to inhibition of gastric acid secretion, it can be concluded that pantoprazole is superior to omeprazole and lansoprazole when unwanted adverse effects with drug metabolizing enzymes are considered. This may be an advantage in clinical use of the drug.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1651432&dopt=Abstract lansoprazole Prevacid



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Effects of the enantiomers of lansoprazole (AG-1749) on (H+ + K+)-ATPase activity in canine gastric microsomes and acid formation in isolated canine parietal cells.

Nagaya H, Inatomi N, Nohara A, Satoh H.

Biology Research Laboratories, Takeda Chemical Industries Ltd, Osaka, Japan.

The effects of the enantiomers of 2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]-sulfinyl ]- 1H-benzimidazole (lansoprazole, AG-1749) on acid formation in isolated canine parietal cells and (H+ + K+)-ATPase activity in canine gastric microsomes were investigated. Both the (+)-and the (-)-enantiomer of lansoprazole inhibited the acid formation stimulated by dibutyryl cyclic AMP (db-cAMP) in isolated canine parietal cells in a concentration-dependent manner with IC50 values of 59 and 82 nM, respectively. The enantiomers showed concentration-dependent inhibition of (H+ + K+)-ATPase with IC50 values of 4.2 and 5.2 microM, respectively. On the other hand, the IC50 values of lansoprazole for db-cAMP-stimulated acid formation and (H+ + K+)-ATPase were 59 nM and 2.1 microM, respectively. These results suggest that the two enantiomers of lansoprazole have antisecretory action due to inhibition of (H+ + K+)-ATPase.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1660270&dopt=Abstract lansoprazole Prevacid