Prevacid
The proton pump inhibitor lansoprazole inhibits rhinovirus infection in cultured human tracheal epithelial cells.

Sasaki T, Yamaya M, Yasuda H, Inoue D, Yamada M, Kubo H, Nishimura H, Sasaki H.

Department of Geriatric and Respiratory Medicine, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.

To examine the effects of lansoprazole, a proton pump inhibitor, on rhinovirus infection in airways, human tracheal epithelial cells were infected with a major subgroup of rhinoviruses, type 14 rhinovirus. Rhinovirus increased the mRNA expression of intercellular adhesion molecule-1 (ICAM-1) in the cells, the major rhinovirus receptor, and the content of the soluble form of ICAM-1 (sICAM-1) and cytokines in supernatants. Lansoprazole reduced supernatant titers and RNA of rhinovirus, the susceptibility to rhinovirus infection, the ICAM-1 mRNA production, the number and fluorescence intensity of acidic endosomes in the cells, and supernatants sICAM-1 and cytokine concentrations including interleukin-1beta. Antibody to interleukin-1beta reduced baseline and rhinovirus-induced ICAM-1 production. These results suggest that lansoprazole inhibits rhinovirus infection by reducing ICAM-1 via partly endogenous production of interleukin-1beta, and by blocking the rhinovirus RNA entry into the endosomes. Lansoprazole may modulate airway inflammation by reducing the production of cytokines and ICAM-1 in rhinovirus infection.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15733557&dopt=Abstract lansoprazole Prevacid



Prevacid
Efficacy and Safety of Lansoprazole in Adolescents with Symptomatic Erosive and Non-erosive Gastroesophageal Reflux Disease.

Fiedorek S, Tolia V, Gold BD, Huang B, Stolle J, Lee C, Gremse D.

*The Pediatric Clinic, P.A., North Little Rock, Arkansas; daggerChildren's Hospital of Michigan, Detroit, Michigan; double daggerDepartment of Pediatrics, Emory University, Atlanta, Georgia; section signAbbott Laboratories, Abbott Park, Illinois; paragraph signTAP Pharmaceutical Products Inc., Lake Forest, Illinois; ||Division of Pediatric Gastroenterology and Nutrition, University of South Alabama College of Medicine, Mobile, Alabama.

OBJECTIVES:: To assess the efficacy and safety of lansoprazole in the treatment of adolescents with symptomatic, endoscopically proven, non-erosive gastroesophageal reflux disease and erosive esophagitis. METHODS:: Adolescents between 12 and 17 years of age with esophagitis were enrolled in this open-label trial and treated with lansoprazole 15 mg (non-erosive) or 30 mg (erosive) once daily for 8 weeks. If unhealed at week 8, those with erosive esophagitis were treated with an additional 4 weeks of lansoprazole 30 mg once daily. RESULTS:: Lansoprazole produced a significant reduction from baseline in the median percentage of days with reflux symptoms (91 to 43% in the 64 adolescents with non-erosive disease and 85 to 16% in the 23 adolescents with erosive esophagitis, P </= 0.001 for each comparison). At week 8, mucosal healing had occurred in 95% (21 of 22) of those with erosive esophagitis. Treatment-related adverse events were reported by 19% of patients with non-erosive and 4% of patients with erosive esophagitis. Headache (7%), abdominal pain (5%), nausea (3%) and dizziness (3%) were the most frequently reported adverse events. One patient discontinued treatment early because of dizziness and vomiting. An elevation in mean serum gastrin from baseline (59 pg/mL at pretreatment to 80 pg/mL at final visit) was observed. CONCLUSION:: Lansoprazole 15 mg or 30 mg once daily reduced symptoms of gastroesophageal reflux in adolescents with non-erosive gastroesophageal reflux disease and erosive esophagitis, respectively. Lansoprazole 30 mg once daily for 8 weeks was effective in healing erosive esophagitis. Both treatment regimens were considered safe.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15735486&dopt=Abstract lansoprazole Prevacid



Prevacid
Effects of clarithromycin on lansoprazole pharmacokinetics between CYP2C19 genotypes.

Saito M, Yasui-Furukori N, Uno T, Takahata T, Sugawara K, Munakata A, Tateishi T.

First Department of Internal Medicine, Hirosaki University School of Medicine, Hirosako, Japan.

Aims Lansoprazole is a substrate of CYP2C19 and CYP3A. The aim of this study was to compare the inhibitory effects of clarithromycin, an inhibitor of CYP3A on the metabolism of lansoprazole between CYP2C19 genotypes. Methods A two-way randomized double-blind, placebo-controlled crossover study was performed. Eighteen volunteers, of whom six were homozygous extensive metabolizers (EMs), six were heterozygous EMs and six were poor metabolizers (PMs) for CYP2C19, received two 6-day courses of either clarithromycin 800 mg or placebo daily in a randomized fashion with a single oral dose of lansoprazole 60 mg on day 6 in all cases. Plasma concentrations of lansoprazole and its metabolites, 5-hydroxylansoprazole and lansoprazole sulphone were monitored up to 24 h after dosing. Results During placebo administration, the mean AUC(0, infinity) of lansoprazole in homozygous EMs, heterozygous EMs and PMs were 4652 (95% CI, 2294, 7009) ng ml(-1) h, 8299 (4784, 11814) ng ml(-1) h and 25293 (17643, 32943) ng ml(-1) h (P < 0.001), respectively. Clarithromycin treatment significantly increased C(max) by 1.47-fold, 1.71-fold and 1.52-fold and AUC(0, infinity) of lansoprazole by 1.55-fold, 1.74-fold, and 1.80-fold in these genotype groups, respectively, whereas elimination half-life was prolonged only in PMs. The clarithromycin-mediated percent increase in pharmacokinetic parameters such as C(max), AUC(0, infinity) or elimination half-life did not differ between the three CYP2C19 genotypes. Conclusions The present study indicates that there are significant drug interactions between lansoprazole and clarithromycin in all CYP2C19 genotype groups probably through CYP3A inhibition. The bioavailability of lansoprazole might, to some extent, be increased through inhibition of P-glycoprotein during clarithromycin treatment.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15752376&dopt=Abstract lansoprazole Prevacid



Prevacid
Role of CYP3A4 and CYP2C19 in the stereoselective metabolism of lansoprazole by human liver microsomes.

Katsuki H, Hamada A, Nakamura C, Arimori K, Nakano M.

Department of Pharmacy, Kumamoto University Hospital, Japan.

OBJECTIVE: The aim of this investigation was to clarify the stereoselective properties in lansoprazole metabolism by monitoring the metabolic consumption for each enantiomer and the formation of the main metabolites, lansoprazole sulfone and 5-hydroxylansoprazole, in the presence of human liver microsomal enzymes. METHODS: Human liver microsomes or recombinant cytochrome P450 (CYP) enzymes were incubated with either (+/- )-, (+)-, or (-)-lansoprazole in the presence of reduced nicotinamide adenine dinucleotide phosphate. The metabolic consumption of lansoprazole enantiomers was estimated from the amounts of enantiomers consumed by microsomal enzymes after incubation at 37 degrees C for 60 min. Metabolites of lansoprazole, lansoprazole sulfone, and 5-hydroxylansoprazole were determined after incubation at 37 degrees C for 20 min, and kinetic parameters [Michaelis constant (Km) and maximum velocity (Vmax)] were obtained using Eadie-Hofstee plots. RESULTS: (-)-Lansoprazole was metabolized more preferentially than (+)-lansoprazole in human liver microsomes. Stereoselective sulfoxidation and hydroxylation [(+) > (-)] were observed in human liver microsomes. Strikingly, in sulfoxidation, a significantly higher intrinsic clearance (Vmax,l/Km,l) of (-)-lansoprazole (0.023 +/- 0.001 ml/min/mg) than (+)-lansoprazole (0.006 +/- 0.000 ml/min/mg) was observed. Consequently, sulfoxidation is likely to play an important role in the stereoselective metabolism of lansoprazole enantiomers. P450-isoform specificity for each enantiomer was evident. CYP3A4, which mainly catalyzed sulfoxidation, was more active toward (-)-lansoprazole in either a chiral or racemic drug as a substrate. CYP2C19, which catalyzed hydroxylation, preferentially metabolized (+)-lansoprazole. The consumption of (+)-lansoprazole was markedly inhibited by (-)-lansoprazole, indicating a metabolic enantiomer/enantiomer interaction. However, this alteration of recombinant CYP2C19 specificity for (+)-lansoprazole did not appear in metabolism in human liver microsomes. CONCLUSIONS: Stereoselective metabolism was observed in human liver microsomes, and this stereoselectivity was mainly based on CYP3A4 specificity for preferable metabolism of (-)-lansoprazole.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11829200&dopt=Abstract lansoprazole Prevacid



Prevacid
Effects of pantoprazole, a novel H+/K+-ATPase inhibitor, on duodenal ulcerogenic and healing responses in rats: a comparative study with omeprazole and lansoprazole.

Takeuchi K, Konaka A, Nishijima M, Kato S, Yasuhiro T.

Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Japan. takeuchi mb.kyoto-phu.ac.jp

BACKGROUND: Pantoprazole, 2-[(2-pyridylmethyl) sulphinyl] benzimidazole, is a new substituted benzimidazole that inhibits the parietal cell H+/K+-ATPase. METHODS: In the present study, the anti-secretory and anti-ulcer activities of pantoprazole were compared with those of omeprazole and lansoprazole in rats. RESULTS: Pantoprazole (0.3-3 mg/kg, p.o.) as well as omeprazole (1-10 mg/kg, p.o.) and lansoprazole (1-10 mg/kg, p.o.) dose-dependently decreased both basal acid secretion in pylorus-ligated rats and the stimulated acid secretion induced by mepirizole in acute fistula rats, and the effects of pantoprazole were more potent than those of omeprazole and lansoprazole, the ED50 values for the stimulated acid secretion being 0.8, 2.0 and 1.2 mg/kg, respectively. Neither of these drugs had any effect on duodenal HCO3- secretion. These pump inhibitors prevented the development of duodenal lesions in response to mepirizole in a dose-related manner, the ED50 values for pantoprazole, omeprazole and lansoprazole being 0.4, 2.0 and 1.3 mg/kg, respectively. Likewise, pantoprazole showed the healing promoting action on chronic duodenal ulcers induced by acetic acid, and this effect was also more potent when compared to omeprazole or lansoprazole. CONCLUSIONS: We conclude that pantoprazole exhibited both anti-ulcer and healing promoting effects on duodenal ulcers in rats, and the effects may be attributable to its potent anti-secretory action. Other pump inhibitors such as omeprazole and lansoprazole were almost equally effective as pantoprazole, yet this drug was most potent on the basis of ED50 values.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10197495&dopt=Abstract lansoprazole Prevacid